Book Description

To build a functional nervous system, neurons must diversify properly, then migrate to their proper locations, establish polarity, extend axons and dendrites in the right directions, and synapse onto specific neuronal targets. When they are born, neurons have an unremarkable shape; as they develop, they acquire complex morphologies that reflect their functions. Here, genetics and microscopy were used to understand neuronal development in Caenorhabditis elegans . We investigated axon formation in the developing HSN motorneuron of C. elegans . The secreted guidance factor UNC-6/netrin and its receptor UNC-40/DCC induce polarized growth of the immature HSN neuron and restrict neurite formation to its ventral surface. Thus netrin defines the direction of polarized neurite outgrowth even before the formation of the axon. Two cytoplasmic proteins, UNC-34/Enabled and MIG-10/Lamellopodin, act as netrin effectors for polarization and ventral guidance. As the HSN axon forms, the PH-domain protein MIG-10 is transiently localized to the ventral side of HSN in a netrin-dependent manner. Neurons lacking either AGE-1/PI3K or DAF-18/PTEN fail to properly localize MIG-10, suggesting that localized lipid signaling downstream of netrin mediates an early step of axon formation.