A midline switch of receptor processing regulates commissural axon guidance in vertebrates
- Homaira Nawabi1,4,
- Anne Briançon-Marjollet1,4,
- Christopher Clark1,
- Isabelle Sanyas1,
- Hyota Takamatsu2,
- Tatsusada Okuno2,
- Atsushi Kumanogoh2,
- Muriel Bozon1,
- Kaori Takeshima3,
- Yutaka Yoshida3,
- Frédéric Moret1,
- Karima Abouzid1 and
- Valérie Castellani1,5
- 1University of Lyon, University of Lyon 1, Claude Bernard Lyon1, CGMC, UMR, CNRS 5534, F-69000 Lyon, France;
- 2Department of Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka, 565-0871, Japan;
- 3Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA
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↵4 These authors contributed equally to this work.
Abstract
Commissural axon guidance requires complex modulations of growth cone sensitivity to midline-derived cues, but underlying mechanisms in vertebrates remain largely unknown. By using combinations of ex vivo and in vivo approaches, we uncovered a molecular pathway controlling the gain of response to a midline repellent, Semaphorin3B (Sema3B). First, we provide evidence that Semaphorin3B/Plexin-A1 signaling participates in the guidance of commissural projections at the vertebrate ventral midline. Second, we show that, at the precrossing stage, commissural neurons synthesize the Neuropilin-2 and Plexin-A1 Semaphorin3B receptor subunits, but Plexin-A1 expression is prevented by a calpain1-mediated processing, resulting in silencing commissural responsiveness. Third, we report that, during floor plate (FP) in-growth, calpain1 activity is suppressed by local signals, allowing Plexin-A1 accumulation in the growth cone and sensitization to Sema3B. Finally, we show that the FP cue NrCAM mediates the switch of Plexin-A1 processing underlying growth cone sensitization to Sema3B. This reveals pathway-dependent modulation of guidance receptor processing as a novel mechanism for regulating guidance decisions at intermediate targets.
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Footnotes
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↵5 Corresponding author.
E-MAIL castellani{at}cgmc.univ-lyon1.fr; FAX 33-0472442685.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.542510.
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Supplemental material is available at http://www.genesdev.org.
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- Received June 5, 2009.
- Accepted December 18, 2009.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press