The somatosensory system detects mechanical, thermal and chemical stimuli; abnormalities in somatosensory signaling can lead to migraine and chronic pain. Neurons within the somatosensory system are specialized to detect different types of sensory stimuli, via expression of various cell surface receptors, development of diverse branching morphologies, and appropriate targeting to the central nervous system. To uncover the molecular mechanisms that generate these differences, we employed genome-wide transcriptional profiling in purified subpopulations of somatosensory neurons. From our list of differentially-expressed candidate genes, we are focusing on secreted peptides, transmembrane proteins, cytoskeletal regulators, and transcription factors for follow-up studies, as these gene families likely regulate development, morphogenesis, and function of somatosensory neurons. We are working to confirm enrichment of these genes in sensory neurons via fluorescence expression analyses, and to identify the neuronal subtypes in which these genes are expressed. Potential functions for the most promising candidates are being identified with genetic gain- and loss-of-function approaches. Specifically, neuronal outgrowth and branching morphology are quantified in embryos in which each candidate gene is overexpressed simultaneously with a fluorescent marker, driven by subtype-specific enhancer sequences. These embryos are also tested for changes in sensory responsiveness via high-throughput videotracking analysis. Similarly, CRISPR-generated knockouts will be analyzed for mutant phenotypes using assays of neuronal morphology and behavioral response to sensory stimuli of various modalities..