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. 2004 Feb 15;18(4):435-47. doi: 10.1101/gad.1167304. Epub 2004 Feb 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Embryonic and Fetal Development
  • Gene Silencing
  • Heart / embryology*
  • Heart Conduction System
  • Mice
  • Morphogenesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • RNA, Messenger / genetics
  • RNA, Small Interfering / physiology
  • Receptors, Cell Surface*
  • Receptors, Peptide / genetics
  • Receptors, Peptide / physiology*
  • Semaphorins / genetics
  • Semaphorins / physiology*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / physiology*

Substances

  • Nerve Tissue Proteins
  • Plxna1 protein, mouse
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Cell Surface
  • Receptors, Peptide
  • Sema6d protein, mouse
  • Semaphorins
  • Vascular Endothelial Growth Factor Receptor-2