Abstract
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.
Highlights
The best known function of Shh (Sonic hedgehog) is its role as a morphogen in the developing spinal cord [1,2,3,4,5,6]
In the dorsal spinal cord, neurons are mainly influenced by Bone Morphogenetic Proteins (BMPs) and members of the Wnt family, secreted by the roof plate [7,8,9,10]
In the hypomorphic Netrin mouse line, some axons still extended toward the floor plate, prompting the question of whether the residual levels of Netrin protein were responsible for their navigation, or whether additional long-range attractants would be released from the floor plate
Summary
The best known function of Shh (Sonic hedgehog) is its role as a morphogen in the developing spinal cord [1,2,3,4,5,6]. In the ventral spinal cord, the floor plate is the source of the ventralizing morphogen Shh. Shh signaling affects cell differentiation by binding to the surface receptor Patched (Ptc). The role of Shh in axon guidance was identified much later than its function in cell differentiation and tissue patterning [12]. Shh was implicated in commissural axon guidance in the spinal cord [14,15,16,17,18]. This role was extended to other populations of neurons [19,20,21,22,23]
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