Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins.
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.
Gu
Chenghua
C
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
Yoshida
Yutaka
Y
Livet
Jean
J
Reimert
Dorothy V
DV
Mann
Fanny
F
Merte
Janna
J
Henderson
Christopher E
CE
Jessell
Thomas M
TM
Kolodkin
Alex L
AL
Ginty
David D
DD
D000818:Animals; D001665:Binding Sites; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D019521:Body Patterning; D019556:COS Cells; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology; D006023:Glycoproteins / Q000378:metabolism*; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D039942:Neuropilin-1 / Q000378:metabolism; D039943:Neuropilin-2 / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D039961:Semaphorins; D015398:Signal Transduction; D019170:Somites / Q000378:metabolism*; D014162:Transfection
D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C473552:Plxnd1 protein, mouse; D011993:Recombinant Fusion Proteins; C111150:Sema3e protein, mouse; D039961:Semaphorins; D039942:Neuropilin-1