Neurotrophin control of sympathetic axon growth

The complexity of nervous system development is astounding: Not only must the organism generate neuron numbers appropriate for the needs of targets being innervated, but it must also instruct these neurons to extend axons, elaborate dendrites, and form synapses in order to ensure the exquisite specificity of connectivity necessary for normal physiological function. The precise coordination of the many events in nervous system development is absolutely critical for the correct establishment of functional circuits. The postganglionic sympathetic neuron has been an amenable model for studying peripheral nervous system formation. Factors that control several events, including axon extension, neuron survival and death, dendritogenesis, synaptogenesis, and establishment of functional diversity, have been identified in this neuron type. However, the molecular control of sympathetic neuron development still presents several intriguing questions. Here, I examine the regulation of sympathetic axon growth and specifically the role of the neurotrophins NGF and NT-3 in sympathetic neuron development. I find that these two related neurotrophins control distinct but successive stages of sympathetic axon growth in vivo and differentially affect sympathetic growth cone morphology and branching in vitro. I identify the small GTPase Rac1 as a candidate for mediating the divergent signaling from NGF and NT-3 via TrkA with potential roles in receptor internalization, cytoskeletal reorganization, and axon growth. These findings add to the extensive knowledge of how sympathetic neurons develop and allow a better integration of the distinct temporal and spatial elements of sympathetic neuron development into a coordinated process that leads from neuron specification to axon growth to maturation, with the ultimate goal of creating a unified paradigm for neuron development.