Sonic Hedgehog regulates Wnt activity during neural circuit formation.

Gradients of secreted morphogens, such as Sonic hedgehog (Shh), Wnt, and TGFβ/Bmp, have classically been shown to control many aspects of early development by regulating cell proliferation and determining cell fate. However, recent studies demonstrate that these molecules also play important and evolutionarily conserved roles in later aspects of neural development. Depending on the context, these molecules can elicit gene transcription in the nucleus, or alternatively can provide instructive signals at the growth cone that induce local and rapid changes in cytoskeletal organization. Shh can activate different cellular transduction pathways via its binding to alternative coreceptor complexes or simply by adaptation of its "classical" signaling pathway. However, in most of its activities during neural development, Shh does not act alone but rather in concert with other morphogens, particularly the Wnts. This review provides an overview of the mechanisms by which Shh signaling acts in concert with Wnts to mediate a myriad of cellular processes that are required for neural circuit formation. Copyright Â