The developmental mechanisms by which functional diversity is achieved in the chemosensory nervous system are poorly understood. The nematode C. elegans responds to its chemical environment using a small and well-defined set of chemosensory neurons, each of which exhibits unique sensory properties and morphology. The goal of this proposal is to arrive at a complete description of the genetic regulatory networks dictating individual chemosensory neuron identities. Specifically, we will: 1) Analyze the genetic cascades specifying the fates of the lineal sibling AWB and ADF chemosensory neurons. We will identify members of the regulatory hierarchies specifying the distinct identities of these 2 neuron types using forward genetic screens, and by expression profiling populations of single neuron types. Identified genes will then be placed in regulatory pathways and networks. 2) Analyze the cis-and trans-regulatory mechanisms driving AWB-and ADF-specific gene expression. We will decipher the cis-regulatory logic driving chemosensory neuron-specific gene expression. Regulatory elements will be identified by both experimental and bioinformatics-based approaches, and additional co-regulated genes will be identified via genome-wide searches. Trans-acting factors directly interacting with defined elements will be identified by a high-throughput 1-hybrid screen and biologically validated. 3) Analyze the developmental mechanisms dictating AWB-specific neuronal morphology. We will identify the molecules and investigate the pathway regulating acquisition of neuron-specific ciliary morphology, and determine how this pathway intersects with pathways regulating additional aspects of cellular identity. We expect that this work will elucidate the transcriptional cascades that act in postmitotic neurons to orchestrate the acquisition of multiple subtype-specific traits. Since many of the molecules and regulatory interactions are conserved across species, this work will provide new information about the roles of conserved proteins in multiple developmental contexts, including in disease. Lay summary: The goal is to understand the developmental principles dictating the generation of specific neuron types using the C. elegans model system. We expect that this information will inform experiments aimed at driving the differentiation of defined cell types from multipotent precursors such as stem cells. ? ? ?
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