A midline switch of receptor processing regulates commissural axon guidance in vertebrates

作者：Nawabi Homaira; Briancon Marjollet Anne; Clark Christopher; Sanyas Isabelle; Takamatsu Hyota; Okuno Tatsusada; Kumanogoh Atsushi; Bozon Muriel; Takeshima Kaori; Yoshida Yutaka; Moret Frederic; Abouzid Karima; Castellani Valerie^*

来源：Genes & Development, 2010, 24(4): 396-410.

DOI：10.1101/gad.542510

• Axon guidance
• midline crossing
• semaphorin
• calpain
• commissural neurons

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.

• 出版日期2010-2-15