Emerging mechanisms in morphogen-mediated axon guidance

Early in animal development, gradients of secreted morphogenic molecules, such as Sonic hedgehog (Shh), Wnt and TGFβ/Bmp family members, regulate cell proliferation and determine the fate and phenotype of the target cells by activating well-characterized signalling pathways, which ultimately control gene transcription. Shh, Wnt and TGFβ/Bmp signalling also play an important and evolutionary conserved role in neural circuit assembly. They regulate neuronal polarization, axon and dendrite development and synaptogenesis, processes that require rapid and local changes in cytoskeletal organization and plasma membrane components. A key question then is whether morphogen signalling at the growth cone uses similar mechanisms and intracellular pathway components to those described for morphogen-mediated cell specification. This review discusses recent advances towards the understanding of this problem, showing how Shh, Wnt and TGFβ/Bmp have adapted their ‘classical’ signalling pathways or adopted alternative and novel molecular mechanisms to influence different aspects of neuronal circuit formation.