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Publication : Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2.

First Author  Toyofuku T Year  2004
Journal  Genes Dev Volume  18
Issue  4 Pages  435-47
PubMed ID  14977921 Mgi Jnum  J:88810
Mgi Id  MGI:3037225 Doi  10.1101/gad.1167304
Citation  Toyofuku T, et al. (2004) Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2. Genes Dev 18(4):435-47
abstractText  Semaphorins, originally identified as axon guidance facto s in the nervous system, play integral roles in organogenesis. Here, we demonstrate a critical involvement of Sema6D in cardiac morphogenesis. Ectopic expression of Sema6D o RNA interference against Sema6D induces expansion or narrowing of the ventricular chamber, respectively, during chick embryonic development. Sema6D also exerts region-specific activities on cardiac explants, a migration-promoting activity on outgrowing cells from the conotruncal segment, and a migration-inhibitory activity on those from the ventricle. Plexin-A1 mediates these activities as the major Sema6D-binding receptor. Plexin-A1 forms a receptor complex with vascular endothelial growth factor receptor type 2 in the conotruncal segment or with Off-track in the ventricle segment; these complexes are responsible for the effects of Sema6D on the respective regions. Thus, the differential association of Plexin-A1 with additional receptor components entitles Sema6D to exert distinct biological activities at adjacent regions. This is crucial for complex cardiac morphogenesis.
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