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As reflected by the term morphogen, molecules such as Shh and Wnts were identified based on their role in early development when they instruct precursor cells to adopt a specific cell fate. Only much later were they implicated in neural circuit formation. Both in vitro and in vivo studies indicated that morphogens direct axons during their navigation through the developing nervous system. Today, the best understood role of Shh and Wnt in axon guidance is their effect on commissural axons in the spinal cord. Shh was shown to affect commissural axons both directly and indirectly via its effect on Wnt signaling. In fact, throughout neural circuit formation there is cross-talk and collaboration of Shh and Wnt signaling. Thus, although the focus of this review is on the role of Shh in neural circuit formation, a separation from Wnt signaling is not possible.

Sonic Hedgehog—‘Jack-of-All-Trades’ in Neural Circuit Formation