In the nervous system, the pattern of synaptic inputs and outputs defines the direction of information flow. A neuron detects stimuli via elongated processes called dendrites and releases signals from a morphologically distinct class of cytoplasmic extensions called axons. These asymmetric features of neurons are developmentally controlled and fundamentally important to brain function. In the nematode, C. elegans, the DD class of GABA motor neurons undergoes a developmentally regulated reversal of synaptic polarity in which a dendrite switches to become an axon and an axon adopts the properties of a dendrite. Remarkably, DD neuronal processes are not withdrawn to accommodate this change but are remodeled in situ to interconvert pre- and post-synaptic specializations. The implementation of this program is regulated by UNC- 55, a conserved member of the COUP family of nuclear hormone receptor transcription factors. Therefore, we hypothesize that polarity reversal and synaptic remodeling of the DD motor neurons are transcriptionally controlled. We will use new, powerful, cell-specific microarray technology to (1) profile DD motor neurons during the developmental period in which metamorphosis occurs and (2) exploit unc-55 mutants to identify UNC-55 regulated transcripts. A comparison of these data sets should reveal strong candidates for genes that orchestrate polarity reversal and the consequent synaptic remodeling of DD motor neurons. The evident plasticity of vertebrate neuronal asymmetry and the evolutionary conservation of molecules that specify neuronal polarity suggest that our discoveries in a nematode model system will reveal genes with fundamental roles in regulating these events. ? ?
