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Sonic hedgehog induces response of commissural axons to Semaphorin repulsion during midline crossing.

Authors: Parra, Liseth M  Zou, Yimin 
Citation: Parra LM and Zou Y, Nat Neurosci. 2010 Jan;13(1):29-35. doi: 10.1038/nn.2457. Epub 2009 Nov 29.
Pubmed: (View Article at PubMed) PMID:19946319
DOI: Full-text: DOI:10.1038/nn.2457

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.

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CRRD Object Information
CRRD ID: 12879429
Created: 2017-04-19
Species: All species
Last Modified: 2017-04-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.