Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.

Vessel growth integrates diverse extrinsic signals with intrinsic signaling cascades to coordinate cell migration and sprouting morphogenesis. The pro-angiogenic effects of Vascular Endothelial Growth Factor (VEGF) are carefully controlled during sprouting to generate an efficiently patterned vascul...

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Autores principales:	Charlene Watterston, Rami Halabi, Sarah McFarlane, Sarah J Childs
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/cd02e6b0683e443196d0ddc66ed48532
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spelling	oai:doaj.org-article:cd02e6b0683e443196d0ddc66ed485322021-12-02T20:02:51ZEndothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.1553-73901553-740410.1371/journal.pgen.1009769https://doaj.org/article/cd02e6b0683e443196d0ddc66ed485322021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009769https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Vessel growth integrates diverse extrinsic signals with intrinsic signaling cascades to coordinate cell migration and sprouting morphogenesis. The pro-angiogenic effects of Vascular Endothelial Growth Factor (VEGF) are carefully controlled during sprouting to generate an efficiently patterned vascular network. We identify crosstalk between VEGF signaling and that of the secreted ligand Semaphorin 3fb (Sema3fb), one of two zebrafish paralogs of mammalian Sema3F. The sema3fb gene is expressed by endothelial cells in actively sprouting vessels. Loss of sema3fb results in abnormally wide and stunted intersegmental vessel artery sprouts. Although the sprouts initiate at the correct developmental time, they have a reduced migration speed. These sprouts have persistent filopodia and abnormally spaced nuclei suggesting dysregulated control of actin assembly. sema3fb mutants show simultaneously higher expression of pro-angiogenic (VEGF receptor 2 (vegfr2) and delta-like 4 (dll4)) and anti-angiogenic (soluble VEGF receptor 1 (svegfr1)/ soluble Fms Related Receptor Tyrosine Kinase 1 (sflt1)) pathway components. We show increased phospho-ERK staining in migrating angioblasts, consistent with enhanced Vegf activity. Reducing Vegfr2 kinase activity in sema3fb mutants rescues angiogenic sprouting. Our data suggest that Sema3fb plays a critical role in promoting endothelial sprouting through modulating the VEGF signaling pathway, acting as an autocrine cue that modulates intrinsic growth factor signaling.Charlene WatterstonRami HalabiSarah McFarlaneSarah J ChildsPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 8, p e1009769 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Charlene Watterston Rami Halabi Sarah McFarlane Sarah J Childs Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.
description	Vessel growth integrates diverse extrinsic signals with intrinsic signaling cascades to coordinate cell migration and sprouting morphogenesis. The pro-angiogenic effects of Vascular Endothelial Growth Factor (VEGF) are carefully controlled during sprouting to generate an efficiently patterned vascular network. We identify crosstalk between VEGF signaling and that of the secreted ligand Semaphorin 3fb (Sema3fb), one of two zebrafish paralogs of mammalian Sema3F. The sema3fb gene is expressed by endothelial cells in actively sprouting vessels. Loss of sema3fb results in abnormally wide and stunted intersegmental vessel artery sprouts. Although the sprouts initiate at the correct developmental time, they have a reduced migration speed. These sprouts have persistent filopodia and abnormally spaced nuclei suggesting dysregulated control of actin assembly. sema3fb mutants show simultaneously higher expression of pro-angiogenic (VEGF receptor 2 (vegfr2) and delta-like 4 (dll4)) and anti-angiogenic (soluble VEGF receptor 1 (svegfr1)/ soluble Fms Related Receptor Tyrosine Kinase 1 (sflt1)) pathway components. We show increased phospho-ERK staining in migrating angioblasts, consistent with enhanced Vegf activity. Reducing Vegfr2 kinase activity in sema3fb mutants rescues angiogenic sprouting. Our data suggest that Sema3fb plays a critical role in promoting endothelial sprouting through modulating the VEGF signaling pathway, acting as an autocrine cue that modulates intrinsic growth factor signaling.
format	article
author	Charlene Watterston Rami Halabi Sarah McFarlane Sarah J Childs
author_facet	Charlene Watterston Rami Halabi Sarah McFarlane Sarah J Childs
author_sort	Charlene Watterston
title	Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.
title_short	Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.
title_full	Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.
title_fullStr	Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.
title_full_unstemmed	Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.
title_sort	endothelial semaphorin 3fb regulates vegf pathway-mediated angiogenic sprouting.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/cd02e6b0683e443196d0ddc66ed48532
work_keys_str_mv	AT charlenewatterston endothelialsemaphorin3fbregulatesvegfpathwaymediatedangiogenicsprouting AT ramihalabi endothelialsemaphorin3fbregulatesvegfpathwaymediatedangiogenicsprouting AT sarahmcfarlane endothelialsemaphorin3fbregulatesvegfpathwaymediatedangiogenicsprouting AT sarahjchilds endothelialsemaphorin3fbregulatesvegfpathwaymediatedangiogenicsprouting
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Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.

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