Semaphorin-plexin signaling guides patterning of the developing vasculature.
Major vessels of the vertebrate circulatory system display evolutionarily conserved and reproducible anatomy, but the cues guiding this stereotypic patterning remain obscure. In the nervous system, axonal pathways are shaped by repulsive cues provided by ligands of the semaphorin family that are sensed by migrating neuronal growth cones through plexin receptors. We show that proper blood vessel pathfinding requires the endothelial receptor PlexinD1 and semaphorin signals, and we identify mutations in plexinD1 in the zebrafish vascular patterning mutant out of bounds. These results reveal the fundamental conservation of repulsive patterning mechanisms between axonal migration in the central nervous system and vascular endothelium during angiogenesis.
Torres-Vázquez
Jesús
J
Laboratory of Molecular Genetics, NICHD, National Institutes of Health, Bethesda, MD 20892, USA.
Gitler
Aaron D
AD
Fraser
Sherri D
SD
Berk
Jason D
JD
Van N  Pham
Fishman
Mark C
MC
Childs
Sarah
S
Epstein
Jonathan A
JA
Weinstein
Brant M
BM
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics*; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D019170:Somites / Q000166:cytology / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C473552:Plxnd1 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins; D029961:Zebrafish Proteins; C488979:plxnd1 protein, zebrafish