Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A.
Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle...
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oai:doaj.org-article:e03a0204fd6c4ff899ff4801bc03f5d92021-11-18T05:37:33ZBrain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A.1544-91731545-788510.1371/journal.pbio.1001808https://doaj.org/article/e03a0204fd6c4ff899ff4801bc03f5d92014-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24618750/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus controlling key physiological functions such as reproduction.Paolo GiacobiniJyoti ParkashCéline CampagneAndrea MessinaFilippo CasoniCharlotte VanackerFanny LangletBarbara HoboGabriella CagnoniSarah GalletNaresh Kumar HanchateDanièle MazurMasahiko TaniguchiMassimiliano MazzoneJoost VerhaagenPhilippe CiofiSébastien G BouretLuca TamagnoneVincent PrevotPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 12, Iss 3, p e1001808 (2014) |
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Biology (General) QH301-705.5 |
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Biology (General) QH301-705.5 Paolo Giacobini Jyoti Parkash Céline Campagne Andrea Messina Filippo Casoni Charlotte Vanacker Fanny Langlet Barbara Hobo Gabriella Cagnoni Sarah Gallet Naresh Kumar Hanchate Danièle Mazur Masahiko Taniguchi Massimiliano Mazzone Joost Verhaagen Philippe Ciofi Sébastien G Bouret Luca Tamagnone Vincent Prevot Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A. |
description |
Neuropilin-1 (Nrp1) guides the development of the nervous and vascular systems, but its role in the mature brain remains to be explored. Here we report that the expression of the 65 kDa isoform of Sema3A, the ligand of Nrp1, by adult vascular endothelial cells, is regulated during the ovarian cycle and promotes axonal sprouting in hypothalamic neurons secreting gonadotropin-releasing hormone (GnRH), the neuropeptide controlling reproduction. Both the inhibition of Sema3A/Nrp1 signaling and the conditional deletion of Nrp1 in GnRH neurons counteract Sema3A-induced axonal sprouting. Furthermore, the localized intracerebral infusion of Nrp1- or Sema3A-neutralizing antibodies in vivo disrupts the ovarian cycle. Finally, the selective neutralization of endothelial-cell Sema3A signaling in adult Sema3aloxP/loxP mice by the intravenous injection of the recombinant TAT-Cre protein alters the amplitude of the preovulatory luteinizing hormone surge, likely by perturbing GnRH release into the hypothalamo-hypophyseal portal system. Our results identify a previously unknown function for 65 kDa Sema3A-Nrp1 signaling in the induction of axonal growth, and raise the possibility that endothelial cells actively participate in synaptic plasticity in specific functional domains of the adult central nervous system, thus controlling key physiological functions such as reproduction. |
format |
article |
author |
Paolo Giacobini Jyoti Parkash Céline Campagne Andrea Messina Filippo Casoni Charlotte Vanacker Fanny Langlet Barbara Hobo Gabriella Cagnoni Sarah Gallet Naresh Kumar Hanchate Danièle Mazur Masahiko Taniguchi Massimiliano Mazzone Joost Verhaagen Philippe Ciofi Sébastien G Bouret Luca Tamagnone Vincent Prevot |
author_facet |
Paolo Giacobini Jyoti Parkash Céline Campagne Andrea Messina Filippo Casoni Charlotte Vanacker Fanny Langlet Barbara Hobo Gabriella Cagnoni Sarah Gallet Naresh Kumar Hanchate Danièle Mazur Masahiko Taniguchi Massimiliano Mazzone Joost Verhaagen Philippe Ciofi Sébastien G Bouret Luca Tamagnone Vincent Prevot |
author_sort |
Paolo Giacobini |
title |
Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A. |
title_short |
Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A. |
title_full |
Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A. |
title_fullStr |
Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A. |
title_full_unstemmed |
Brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3A. |
title_sort |
brain endothelial cells control fertility through ovarian-steroid-dependent release of semaphorin 3a. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doaj.org/article/e03a0204fd6c4ff899ff4801bc03f5d9 |
work_keys_str_mv |
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