Letter abstract
Nature Cell Biology 6, 1204 - 1211 (2004)
Published online: 14 November 2004 | doi:10.1038/ncb1193
Guidance of myocardial patterning in cardiac development by Sema6D reverse signalling
Toshihiko Toyofuku1,2,3, Hong Zhang1,2, Atsushi Kumanogoh2,3, Noriko Takegahara2, Masanori Yabuki1,2, Koichiro Harada1,2, Masatsugu Hori1 & Hitoshi Kikutani2,3
Cardiac chamber formation involves dynamic changes in myocardial organization, including trabeculation and expansion of the compact layer1. The positional cues that regulate myocardial patterning, however, remain unclear. Through ligation of the Plexin-A1 receptor, the transmembrane-type semaphorin Sema6D regulates endocardial cell migration2. Here, we demonstrate that knockdown of either Sema6D or Plexin-A1 leads to the generation of a small, thin ventricular compact layer and to defective trabeculation. In the heart, expression of the Plexin-A1 extracellular domain alone can rescue the defective trabeculation induced by suppression of Plexin-A1, but not that resulting from defective Sema6D expression. This indicates that reverse signalling by Sema6D occurs within the myocardium. In a ligand-dependent manner, Abl kinase is recruited to the cytoplasmic tail of Sema6D and activated, resulting in phosphorylation of Enabled and dissociation from Sema6D. Constitutive activation of Sema6D signalling enhances the migration of myocardial cells into the trabeculae, whereas inhibition arrests cells within the compact layer. Thus, Sema6D coordinates both compact-layer expansion and trabeculation, functioning as both a ligand and a receptor for Plexin-A1.
- Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
- Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
- CREST, Japan Science and Technology Corporation, Japan.
Correspondence to: Hitoshi Kikutani2,3 e-mail: kikutani@ragtime.biken.osaka-u.ac.jp
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Invasive growth: A two-way street for semaphorin signallingNature Cell Biology News and Views (01 Dec 2004)
