| First Author | Nawabi H | Year | 2010 |
| Journal | Genes Dev | Volume | 24 |
| Issue | 4 | Pages | 396-410 |
| PubMed ID | 20159958 | Mgi Jnum | J:156992 |
| Mgi Id | MGI:4429724 | Doi | 10.1101/gad.542510 |
| Citation | Nawabi H, et al. (2010) A midline switch of receptor processing regulates commissural axon guidance in vertebrates. Genes Dev 24(4):396-410 |
| abstractText | 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. |
