CIDeRplusGeneral Information:
| Id: | 9,701 |
| Diseases: |
Cardiovascular disease
Ciliopathy |
| Mammalia | |
| review | |
| Reference: | Klena NT et al.Cilia and Ciliopathies in Congenital Heart Disease [PMID: 28159874] |
Interaction Information:
| Comment | A central role for cilia in congenital heart disease (CHD) was identified in a large-scale mouse mutagenesis screen. Although the screen was phenotype-driven, the majority of genes recovered were cilia-related, suggesting that cilia play a central role in CHD pathogenesis. |
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Formal Description Interaction-ID: 102363 |
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| Comment | Further indicating the important role of cilia in CHD pathogenesis, mutations in 12 CHD genes that are in cilia-transduced cell signaling pathways were recovered , including genes mediating sonic hedgehog (Shh), transforming growth factor beta and bone morphogenetic proteins (TGF-beta/BMPs), and Wnt signaling. |
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Formal Description Interaction-ID: 102485 |
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| Comment | Further indicating the important role of cilia in CHD pathogenesis, mutations in 12 CHD genes that are in cilia-transduced cell signaling pathways were recovered , including genes mediating sonic hedgehog (Shh), transforming growth factor beta and bone morphogenetic proteins (TGF-beta/BMPs), and Wnt signaling. |
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Formal Description Interaction-ID: 102486 |
cellular component affects_activity of |
| Comment | Further indicating the important role of cilia in CHD pathogenesis, mutations in 12 CHD genes that are in cilia-transduced cell signaling pathways were recovered , including genes mediating sonic hedgehog (Shh), transforming growth factor beta and bone morphogenetic proteins (TGF-beta/BMPs), and Wnt signaling. |
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Formal Description Interaction-ID: 102487 |
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| Comment | Further indicating the important role of cilia in CHD pathogenesis, mutations in 12 CHD genes that are in cilia-transduced cell signaling pathways were recovered , including genes mediating sonic hedgehog (Shh), transforming growth factor beta and bone morphogenetic proteins (TGF-beta/BMPs), and Wnt signaling. |
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Formal Description Interaction-ID: 102488 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102489 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102490 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102491 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102492 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102493 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102494 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102495 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102496 |
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| Drugbank entries | Show/Hide entries for LRP1 |
| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102497 |
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| Drugbank entries | Show/Hide entries for LRP2 |
| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102498 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102499 |
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| Comment | Unexpected was the recovery of 10 CHD genes involved in vesicular trafficking. This included Dynamin 2 and Ap2b1 required for clathrin-mediated endocytosis, adaptin proteins Ap1b1 and Ap2b1, and Lrp1, Lrp2, and Snx17 mediating endocytic receptor recycling. Significantly, vesicular trafficking plays an essential role in cilia biology, with ciliogenesis initiated with capture of a ciliary vesicle by the mother centriole followed by docking of the basal body to the cell membrane and fusion of additional secondary vesicles that allow lengthening of the ciliary axoneme. Vesicular trafficking and receptor recycling also play important roles in the regulation of cell signaling. Although the endocytic pathway was not previously known to play a role in CHD, its importance can be easily appreciated in the context of its role in regulating ciliogenesis and cilia-transduced cell signaling. |
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Formal Description Interaction-ID: 102500 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102501 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102502 |
affects_activity of |
| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102503 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102504 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102505 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102506 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102507 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102508 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102509 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102510 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102511 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102512 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102513 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102514 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102515 |
gene/protein affects_activity of |
| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102516 |
gene/protein affects_activity of |
| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102517 |
gene/protein affects_activity of |
| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102518 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102519 |
gene/protein affects_activity of |
| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102520 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102521 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102522 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102523 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102524 |
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| Comment | A numberof cilia-transduced cell signaling pathways have been shown to play essential roles in regulating cardiovascular development and may contribute to the pathogenesis of CHD. These include Shh, TGF-beta, BMP, and Wnt signaling. Four genes involved in Shh signaling were recovered from the mouse CHD screen, including Sufu, Fuz, Tbc1d32, and Kif7. Also recovered were six genes involved in TGF-beta/BMP signaling, including Cfc1, Megf8, Tab1, Ltbp1, Smad6, and Pcsk5 and three mediating Wnt signaling - Ptk7, Prickle1, and Fuz. |
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Formal Description Interaction-ID: 102525 |
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| Comment | Shh signaling is the best-described cilia-transduced cell signaling pathway. Numerous studies have shown that ablation of cilia can result in a drastic reduction of Shh signaling. During heart development, Shh is expressed in the pharyngeal endoderm and in the foregut endoderm adjacent to incoming SHF derivatives in the dorsal mesenchyme protrusion. |
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Formal Description Interaction-ID: 102526 |
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| Comment | Shh knockout mice show atrial and atrioventricular septation defects, defects in OFT septation, and abnormal pharyngeal arch artery patterning. The outflow septation defects are characterized by the aorta shifted right-ward overriding the septum, and with either pulmonary atresia or a hypoplastic pulmonary artery observed in conjunction with a variable degree of ventricular hypertrophy. This constellation of defects is reminiscent of tetralogy of Fallot (TOF), one of the most common complex CHD observed clinically. |
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Formal Description Interaction-ID: 102527 |
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| Comment | Shh knockout mice show atrial and atrioventricular septation defects, defects in OFT septation, and abnormal pharyngeal arch artery patterning. The outflow septation defects are characterized by the aorta shifted right-ward overriding the septum, and with either pulmonary atresia or a hypoplastic pulmonary artery observed in conjunction with a variable degree of ventricular hypertrophy. This constellation of defects is reminiscent of tetralogy of Fallot (TOF), one of the most common complex CHD observed clinically. |
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Formal Description Interaction-ID: 102528 |
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| Comment | Shh knockout mice show atrial and atrioventricular septation defects, defects in outflow tract (OFT) septation, and abnormal pharyngeal arch artery patterning. The outflow septation defects are characterized by the aorta shifted right-ward overriding the septum, and with either pulmonary atresia or a hypoplastic pulmonary artery observed in conjunction with a variable degree of ventricular hypertrophy. This constellation of defects is reminiscent of tetralogy of Fallot (TOF), one of the most common complex CHD observed clinically. |
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Formal Description Interaction-ID: 102529 |
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| Comment | Shh knockout mice show atrial and atrioventricular septation defects, defects in outflow tract (OFT) septation, and abnormal pharyngeal arch artery patterning. The outflow septation defects are characterized by the aorta shifted right-ward overriding the septum, and with either pulmonary atresia or a hypoplastic pulmonary artery observed in conjunction with a variable degree of ventricular hypertrophy. This constellation of defects is reminiscent of tetralogy of Fallot (TOF), one of the most common complex CHD observed clinically. |
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Formal Description Interaction-ID: 102530 |
process affects_activity of phenotype abnormal pharyngeal arch artery patterning |
| Comment | Primary cilia also play a role in the transduction of canonical and non-canonical Wnt signaling, pathways that are also essential for normal heart development. |
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Formal Description Interaction-ID: 102531 |
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| Comment | Primary cilia also play a role in the transduction of canonical and non-canonical Wnt signaling, pathways that are also essential for normal heart development. |
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Formal Description Interaction-ID: 102532 |
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| Comment | Primary cilia also play a role in the transduction of canonical and non-canonical Wnt signaling, pathways that are also essential for normal heart development. |
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Formal Description Interaction-ID: 102533 |
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| Comment | Primary cilia also play a role in the transduction of canonical and non-canonical Wnt signaling, pathways that are also essential for normal heart development. |
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Formal Description Interaction-ID: 102534 |
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| Comment | In mice, the noncanonical Wnt/PCP genes such as Celsr, Frizzled3 (Fzd3), Fzd6, Vangl1-2, and Dvl1-3 are highly expressed in the outflow tract (OFT). Mice with mutations in the PCP genes Vangl2, Scrib, Dvl 1, 2, and 3, Wdpcp, and Pk1 show a spectrum of CHD phenotypes involving OFT malalignment and septation defects, such as double outlet RV, overriding aorta, pulmonary atresia, and persistent truncus arteriosus. These cardiac defects likely reflect a role for noncanonical Wnt/PCP pathway in regulating the polarized migration of cardiac neural crest and SHF derivatives. Consistent with this, examination of mouse embryonic fibroblasts derived from the Wdpcp or Pk1 mutant embryos showed inability of the cells to polarize and engage in directional cell migration. In contrast to Shh deficiency, Wnt/PCP disruption caused failure of the OFT to appropriately lengthen. |
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Formal Description Interaction-ID: 102535 |
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| Comment | In mice, the noncanonical Wnt/PCP genes such as Celsr, Frizzled3 (Fzd3), Fzd6, Vangl1-2, and Dvl1-3 are highly expressed in the outflow tract (OFT). Mice with mutations in the PCP genes Vangl2, Scrib, Dvl 1, 2, and 3, Wdpcp, and Pk1 show a spectrum of CHD phenotypes involving OFT malalignment and septation defects, such as double outlet RV, overriding aorta, pulmonary atresia, and persistent truncus arteriosus. These cardiac defects likely reflect a role for noncanonical Wnt/PCP pathway in regulating the polarized migration of cardiac neural crest and SHF derivatives. Consistent with this, examination of mouse embryonic fibroblasts derived from the Wdpcp or Pk1 mutant embryos showed inability of the cells to polarize and engage in directional cell migration. In contrast to Shh deficiency, Wnt/PCP disruption caused failure of the OFT to appropriately lengthen. |
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Formal Description Interaction-ID: 102536 |
|
| Comment | In mice, the noncanonical Wnt/PCP genes such as Celsr, Frizzled3 (Fzd3), Fzd6, Vangl1-2, and Dvl1-3 are highly expressed in the outflow tract (OFT). Mice with mutations in the PCP genes Vangl2, Scrib, Dvl 1, 2, and 3, Wdpcp, and Pk1 show a spectrum of CHD phenotypes involving OFT malalignment and septation defects, such as double outlet RV, overriding aorta, pulmonary atresia, and persistent truncus arteriosus. These cardiac defects likely reflect a role for noncanonical Wnt/PCP pathway in regulating the polarized migration of cardiac neural crest and SHF derivatives. Consistent with this, examination of mouse embryonic fibroblasts derived from the Wdpcp or Pk1 mutant embryos showed inability of the cells to polarize and engage in directional cell migration. In contrast to Shh deficiency, Wnt/PCP disruption caused failure of the OFT to appropriately lengthen. |
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Formal Description Interaction-ID: 102537 |
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| Comment | In mice, the noncanonical Wnt/PCP genes such as Celsr, Frizzled3 (Fzd3), Fzd6, Vangl1-2, and Dvl1-3 are highly expressed in the outflow tract (OFT). Mice with mutations in the PCP genes Vangl2, Scrib, Dvl 1, 2, and 3, Wdpcp, and Pk1 show a spectrum of CHD phenotypes involving OFT malalignment and septation defects, such as double outlet RV, overriding aorta, pulmonary atresia, and persistent truncus arteriosus. These cardiac defects likely reflect a role for noncanonical Wnt/PCP pathway in regulating the polarized migration of cardiac neural crest and SHF derivatives. Consistent with this, examination of mouse embryonic fibroblasts derived from the Wdpcp or Pk1 mutant embryos showed inability of the cells to polarize and engage in directional cell migration. In contrast to Shh deficiency, Wnt/PCP disruption caused failure of the OFT to appropriately lengthen. |
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Formal Description Interaction-ID: 102538 |
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| Comment | In mice, the noncanonical Wnt/PCP genes such as Celsr, Frizzled3 (Fzd3), Fzd6, Vangl1-2, and Dvl1-3 are highly expressed in the outflow tract (OFT). Mice with mutations in the PCP genes Vangl2, Scrib, Dvl 1, 2, and 3, Wdpcp, and Pk1 show a spectrum of CHD phenotypes involving OFT malalignment and septation defects, such as double outlet RV, overriding aorta, pulmonary atresia, and persistent truncus arteriosus. These cardiac defects likely reflect a role for noncanonical Wnt/PCP pathway in regulating the polarized migration of cardiac neural crest and SHF derivatives. Consistent with this, examination of mouse embryonic fibroblasts derived from the Wdpcp or Pk1 mutant embryos showed inability of the cells to polarize and engage in directional cell migration. In contrast to Shh deficiency, Wnt/PCP disruption caused failure of the OFT to appropriately lengthen. |
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Formal Description Interaction-ID: 102539 |
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| Comment | In mice, the noncanonical Wnt/PCP genes such as Celsr, Frizzled3 (Fzd3), Fzd6, Vangl1-2, and Dvl1-3 are highly expressed in the outflow tract (OFT). Mice with mutations in the PCP genes Vangl2, Scrib, Dvl 1, 2, and 3, Wdpcp, and Pk1 show a spectrum of CHD phenotypes involving OFT malalignment and septation defects, such as double outlet RV, overriding aorta, pulmonary atresia, and persistent truncus arteriosus. These cardiac defects likely reflect a role for noncanonical Wnt/PCP pathway in regulating the polarized migration of cardiac neural crest and SHF derivatives. Consistent with this, examination of mouse embryonic fibroblasts derived from the Wdpcp or Pk1 mutant embryos showed inability of the cells to polarize and engage in directional cell migration. In contrast to Shh deficiency, Wnt/PCP disruption caused failure of the OFT to appropriately lengthen. |
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Formal Description Interaction-ID: 102540 |
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| Comment | In mice, the noncanonical Wnt/PCP genes such as Celsr, Frizzled3 (Fzd3), Fzd6, Vangl1-2, and Dvl1-3 are highly expressed in the outflow tract (OFT). Mice with mutations in the PCP genes Vangl2, Scrib, Dvl 1, 2, and 3, Wdpcp, and Pk1 show a spectrum of CHD phenotypes involving OFT malalignment and septation defects, such as double outlet RV, overriding aorta, pulmonary atresia, and persistent truncus arteriosus. These cardiac defects likely reflect a role for noncanonical Wnt/PCP pathway in regulating the polarized migration of cardiac neural crest and SHF derivatives. Consistent with this, examination of mouse embryonic fibroblasts derived from the Wdpcp or Pk1 mutant embryos showed inability of the cells to polarize and engage in directional cell migration. In contrast to Shh deficiency, Wnt/PCP disruption caused failure of the OFT to appropriately lengthen. |
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Formal Description Interaction-ID: 102541 |
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| Comment | A role for cilia in mediating TGF-beta signaling was recently shown with the finding that ligand binding causes accumulation of TGF-beta receptors at the base of the cilium, in a region known as the ciliary pocket. This triggers receptor-mediated endocytosis involving clathrin-coated vesicles, leading to down-stream activation of SMAD phosphorylation. The essential role of TGF-beta/BMP signaling in CHD is well described via in vitro and in vivo analyses of chick and mouse embryos, and also with the examination of knockout mouse models. These studies show TGF-beta/BMP signaling has multiple roles in cardiovascular development that include the regulation of both endocardial EMT and endocardial cushion development. |
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Formal Description Interaction-ID: 102542 |
affects_activity of disease Congenital heart disease |
| Comment | Although the role of cilia in the regulation of cell polarity and directional cell migration in the cardiovascular development is well described in the context of OFT morphogenesis, the precise mechanism and role of the cilia in modulating cell polarity is less understood. |
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Formal Description Interaction-ID: 102543 |
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| Comment | It is worth pointing out that Wdpcp, a PCP component also known as Fritz, is localized not only in the cilia, but it is also colocalized with septins in the cilia and in the actin cytoskeleton. In mouse embryonic fibroblast (MEF) cells deficient in Wdpcp, a marked reorganization of the actin cytoskeleton is observed, and this is associated with altered focal contacts inability to establish cell polarity and engage in directional cell migration. |
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Formal Description Interaction-ID: 102544 |
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| Comment | The enrichment of cilia genes was also notable in that it included a subset of genes that caused CHD in conjunction with left‚Äďright patterning defects. This likely reflects the known requirement for cilia in left‚Äďright patterning, with previous studies indicating that motile cilia at the embryonic node is required to break symmetry. Analysis of motile cilia mutant mice revealed CHD is typically observed in conjunction with heterotaxy, the randomization of left‚Äďright patterning. This is consistent with the well-described clinical association of complex CHD with heterotaxy. As the heart is the most left‚Äďright asymmetric organ, and this asymmetry is essential for efficient oxygenation of blood, it is perhaps not surprising that left‚Äďright patterning defects may play a major role in CHD pathogenesis. |
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Formal Description Interaction-ID: 102545 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102546 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102547 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102548 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102549 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102550 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102551 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102552 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102553 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102554 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102555 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102556 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102557 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102558 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102559 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102560 |
|
| Comment | Among 34 cilia mutations recovered causing laterality defects, 22 genes perturbed the primary cilia (Cc2d2a, Anks6, Nek8, Mks1, Cep290, Bicc1) versus 12 genes that disrupted motile cilia (Dnah5, Dnah11, Dnai1, Daw1, Armc4, Ccdc151, Drc1, Ccdc39, Dyxc1x1, Dnaaf3). The latter genes are known tocause PCD, a ciliopathy that is autosomal recessive. In PCD, immotile/dyskinetic cilia in the airway cause mucociliary clearance defects that can lead to severe sinopulmonary disease. Approximately half of PCD patients show situs solitus, half situs inversus totalis, and varying numbers up to 8% may show CHD with heterotaxy. The disturbance of laterality with PCD reflects the essential role of motile cilia in left‚Äďright patterning. Studies in the PCD mutant mouse models showed each PCD mutation can give rise to three phenotypes, approximately half with situs solitus or situs inversus and half with heterotaxy, with complex CHD observed only with heterotaxy. |
|
Formal Description Interaction-ID: 102561 |
|
| Comment | Signaling mediated by the TGF-beta family of growth factors, including nodal, lefty1, and lefty2, are well described to specify the left‚Äďright axis. |
|
Formal Description Interaction-ID: 102562 |
|
| Comment | Signaling mediated by the TGF-beta family of growth factors, including nodal, lefty1, and lefty2, are well described to specify the left‚Äďright axis. |
|
Formal Description Interaction-ID: 102563 |
|
| Comment | Signaling mediated by the TGF-beta family of growth factors, including nodal, lefty1, and lefty2, are well described to specify the left‚Äďright axis. |
|
Formal Description Interaction-ID: 102564 |
|
| Comment | A central role for cilia in congenital heart disease (CHD) was identified in a large-scale mouse mutagenesis screen. Although the screen was phenotype-driven, the majority of genes recovered were cilia-related, suggesting that cilia play a central role in CHD pathogenesis. |
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Formal Description Interaction-ID: 102565 |
|