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Published Online November 18, 2004
Science DOI: 10.1126/science.1105416

Reports

Submitted on September 20, 2004
Accepted on November 9, 2004

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

Chenghua Gu 1, Yutaka Yoshida 2, Jean Livet 3, Dorothy V. Reimert 1, Fanny Mann 3, Janna Merte 4, Christopher E. Henderson 3, Thomas M. Jessell 2, Alex L. Kolodkin 5*, David D. Ginty 1*

1 The Department of Neuroscience; Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2 The Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, NY, USA.
3 INSERM UMR623, Developmental Biology Institute of Marseille (IBDM), France.
4 The Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
5 The Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

* To whom correspondence should be addressed.
Alex L. Kolodkin , E-mail: kolodkin{at}jhmi.edu
David D. Ginty , E-mail: dginty{at}jhmi.edu

The development of a patterned vasculature is essential for normal organogenesis. We find 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, presumed obligate Sema3 co-receptors. 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.


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