| First Author | Parra LM | Year | 2010 |
| Journal | Nat Neurosci | Volume | 13 |
| Issue | 1 | Pages | 29-35 |
| PubMed ID | 19946319 | Mgi Jnum | J:156777 |
| Mgi Id | MGI:4421353 | Doi | 10.1038/nn.2457 |
| Citation | Parra LM, et al. (2010) Sonic hedgehog induces response of commissural axons to Semaphorin repulsion during midline crossing. Nat Neurosci 13(1):29-35 |
| abstractText | Pathfinding axons change responses to guidance cues at intermediate targets. During midline crossing, spinal cord commissural axons acquire responsiveness to class 3 Semaphorins and Slits, which regulate their floor plate exit and restrict their post-crossing trajectory into a longitudinal pathway. We found that Sonic Hedgehog (Shh) could activate the repulsive response of pre-crossing axons to Semaphorins. Blocking Shh function with a monoclonal antibody to Shh, 5E1, in 'open-book' explants or by expressing a dominant-negative form of Patched-1, Ptch1(Delta loop2), or a Smoothened (Smo) shRNA construct in commissural neurons resulted in severe guidance defects, including stalling and knotting inside the floor plate, recrossing, randomized anterior-posterior projection and overshooting after crossing, reminiscent of Neuropilin-2 mutant embryos. Enhancing protein kinase A activity in pre-crossing axons diminished Shh-induced Semaphorin repulsion and caused profound midline stalling and overshooting/wandering of post-crossing axons. Therefore, a morphogen, Shh, can act as a switch of axon guidance responses. |
