Transcriptional control of neuronal plasticity by daf-16/FoxO

Many neurons display the remarkable ability to alter specific phenotypic properties in response to changes in the internal or external environment. Such ?neuronal plasticity? phenomena must intersect with genetically hardwired regulatory programs that define the fully differentiated state of a neuron. We propose here to investigate how such hardwired gene regulatory programs are modified to enable the nervous system to change specific phenotypic aspects of a neuron under specific conditions. We study this problem with single neuron resolution in the context of the nematode C. elegans whose nervous system remodels a number of features in response to the phylogenetically conserved insulin/IGF1-like hormonal signaling system. We propose and test in this grant proposal that the insulin/IGF-1-controlled DAF-16/FoxO transcription factors acts cell autonomously in many different neuron types to control the expression of specific target genes that are up- or downregulated in response to specific environmental conditions. We propose and test that DAF-16/FoxO cooperates with neuron-type specific terminal selector transcription to either promote or antagonize the ability of these transcription factors to control their effector genes.