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Science 307 (5707): 265-268

Copyright © 2005 by the American Association for the Advancement of Science

Semaphorin 3E and Plexin-D1 Control Vascular Pattern Independently of Neuropilins

Chenghua Gu,1,2* Yutaka Yoshida,3* Jean Livet,4 Dorothy V. Reimert,1,2 Fanny Mann,4 Janna Merte,1,2 Christopher E. Henderson,4 Thomas M. Jessell,3 Alex L. Kolodkin,1{dagger} David D. Ginty1,2{dagger}

Abstract: The development of a patterned vasculature is essential for normal organogenesis. We found that signaling by semaphorin 3E (Sema3E) and its receptor plexin-D1 controls endothelial cell positioning and the patterning of the developing vasculature in the mouse. Sema3E is highly expressed in developing somites, where it acts as a repulsive cue for plexin-D1–expressing endothelial cells of adjacent intersomitic vessels. Sema3E–plexin-D1 signaling did not require neuropilins, which were previously presumed to be obligate Sema3 coreceptors. Moreover, genetic ablation of Sema3E or plexin-D1 but not neuropilin-mediated Sema3 signaling disrupted vascular patterning. These findings reveal an unexpected semaphorin signaling pathway and define a mechanism for controlling vascular patterning.

1 The Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205–2185, USA.
2 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205–2185, USA.
3 Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA.
4 Institut National de la Santé et de la Recherche Médicale (INSERM), UMR623, Developmental Biology Institute of Marseille (IBDM), Marseille 13288, France.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dginty{at}jhmi.edu (D.D.G.); kolodkin{at}jhmi.edu (A.L.K.)

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