A midline switch of receptor processing regulates commissural axon guidance in vertebrates.
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.
University of Lyon, University of Lyon 1, Claude Bernard Lyon1, CGMC, UMR, CNRS 5534, F-69000 Lyon, France.
Homaira
H
Nawabi
Anne
A
Briançon-Marjollet
Christopher
C
Clark
Isabelle
I
Sanyas
Hyota
H
Takamatsu
Tatsusada
T
Okuno
Atsushi
A
Kumanogoh
Muriel
M
Bozon
Kaori
K
Takeshima
Yutaka
Y
Yoshida
Frédéric
F
Moret
Karima
K
Abouzid
Valérie
V
Castellani
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002154:Calpain / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002642:Chick Embryo; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D039943:Neuropilin-2 / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism; D015398:Signal Transduction
D015815:Cell Adhesion Molecules; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; D039961:Semaphorins; C091529:plexin; D002154:Calpain