Antagonistic interactions among Plexins regulate the timing of intersegmental vessel formation.
The angioblast is an embryonic endothelial cell precursor that migrates long distances to reach its final position, navigating by sensing attractive and repulsive cues from the environment. Members of the semaphorin family have been implicated in controlling the behaviour of angioblast tip cells through repulsive signalling in vitro, but their in vivo roles are less clear. Here we show that zebrafish semaphorin3e (sema3e) is expressed by endothelial cells of the dorsal aorta, primary motoneurons, and endodermal cells. Further, loss of Sema3e leads to delayed exit of angioblasts from the dorsal aorta in ISV formation. Through transplant analysis, we show that Sema3e acts autonomously and non-autonomously in angioblasts to modulate interactions among themselves. The semaphorin receptors, PlexinD1 and PlexinB2, are expressed by zebrafish angioblasts. Loss of plxnB2 results in delayed ISV sprouting identical to that seen in sema3e morphants, while loss of plexinD1 in out of bounds (obd) mutants results in precocious ISV sprouting. Loss of either sema3e or plxnB2 in obd mutants generates an intermediate phenotype, suggesting that PlxnD1 and Sema3e/PlxnB2 antagonize each other to control timing of ISV sprouting. Consistent with this observation, we show that PlxnB2 acts cell autonomously in endothelial cells. This suggests a model where multiple semaphorin-plexin interactions control angioblast sprouting behaviour.
Department of Biochemistry and Molecular Biology, University of Calgary, Canada.
Ryan E
RE
Lamont
Erica J
EJ
Lamont
Sarah J
SJ
Childs
D000818:Animals; D001011:Aorta / Q000196:embryology / Q000502:physiology; D019521:Body Patterning / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000196:embryology / Q000502:physiology*; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D039961:Semaphorins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D002352:Carrier Proteins; D011956:Receptors, Cell Surface; C543912:Sema3E protein, zebrafish; D039961:Semaphorins; D029961:Zebrafish Proteins; C543911:plexin B2, zebrafish; C488979:plxnd1 protein, zebrafish