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Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing

Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-...

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Autores principales: Hernandez-Enriquez, Berenice, Wu, Zhuhao, Martinez, Edward, Olsen, Olav, Kaprielian, Zaven, Maness, Patricia F., Yoshida, Yutaka, Tessier-Lavigne, Marc, Tran, Tracy S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699389/
https://www.ncbi.nlm.nih.gov/pubmed/26680304
http://dx.doi.org/10.1101/gad.268086.115
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author Hernandez-Enriquez, Berenice
Wu, Zhuhao
Martinez, Edward
Olsen, Olav
Kaprielian, Zaven
Maness, Patricia F.
Yoshida, Yutaka
Tessier-Lavigne, Marc
Tran, Tracy S.
author_facet Hernandez-Enriquez, Berenice
Wu, Zhuhao
Martinez, Edward
Olsen, Olav
Kaprielian, Zaven
Maness, Patricia F.
Yoshida, Yutaka
Tessier-Lavigne, Marc
Tran, Tracy S.
author_sort Hernandez-Enriquez, Berenice
collection PubMed
description Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-A1 are also coexpressed on commissural axons prior to midline crossing and can mediate precrossing semaphorin-induced repulsion in vitro. How premature semaphorin-induced repulsion of precrossing axons is suppressed in vivo is not known. We discovered that a novel source of floor plate-derived, but not axon-derived, neuropilin-2 is required for precrossing axon pathfinding. Floor plate-specific deletion of neuropilin-2 significantly reduces the presence of precrossing axons in the ventral spinal cord, which can be rescued by inhibiting plexin-A1 signaling in vivo. Our results show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons.
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spelling pubmed-46993892016-06-15 Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing Hernandez-Enriquez, Berenice Wu, Zhuhao Martinez, Edward Olsen, Olav Kaprielian, Zaven Maness, Patricia F. Yoshida, Yutaka Tessier-Lavigne, Marc Tran, Tracy S. Genes Dev Research Paper Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-A1 are also coexpressed on commissural axons prior to midline crossing and can mediate precrossing semaphorin-induced repulsion in vitro. How premature semaphorin-induced repulsion of precrossing axons is suppressed in vivo is not known. We discovered that a novel source of floor plate-derived, but not axon-derived, neuropilin-2 is required for precrossing axon pathfinding. Floor plate-specific deletion of neuropilin-2 significantly reduces the presence of precrossing axons in the ventral spinal cord, which can be rescued by inhibiting plexin-A1 signaling in vivo. Our results show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons. Cold Spring Harbor Laboratory Press 2015-12-15 /pmc/articles/PMC4699389/ /pubmed/26680304 http://dx.doi.org/10.1101/gad.268086.115 Text en © 2015 Hernandez-Enriquez et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Hernandez-Enriquez, Berenice
Wu, Zhuhao
Martinez, Edward
Olsen, Olav
Kaprielian, Zaven
Maness, Patricia F.
Yoshida, Yutaka
Tessier-Lavigne, Marc
Tran, Tracy S.
Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
title Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
title_full Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
title_fullStr Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
title_full_unstemmed Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
title_short Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
title_sort floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699389/
https://www.ncbi.nlm.nih.gov/pubmed/26680304
http://dx.doi.org/10.1101/gad.268086.115
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