Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing
- Berenice Hernandez-Enriquez1,6,
- Zhuhao Wu2,6,
- Edward Martinez1,
- Olav Olsen2,
- Zaven Kaprielian3,
- Patricia F. Maness4,
- Yutaka Yoshida5,
- Marc Tessier-Lavigne2 and
- Tracy S. Tran1
- 1Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA;
- 2Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065, USA;
- 3Amgen, Cambridge, Massachusetts 02141, USA;
- 4Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA;
- 5Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
- Corresponding author: tstran{at}rutgers.edu
-
↵6 These authors contributed equally to this work.
Abstract
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.
Keywords
Footnotes
-
Supplemental material is available for this article.
-
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.268086.115.
- Received June 27, 2015.
- Accepted November 13, 2015.
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/.