The investigator's long-term goal is to understand how neural crest cells become different from one another, and generate such distinct cell types as neurons, glia, pigment cells and cartilage. Understanding at the molecular level how cells become specified is not only important for determining the proper construction of complex structures such as the nervous system, but is critical for understanding what goes awry in birth defects, or what happens when cells lose growth control in cancer. Understanding of the events leading to the formation of a functioning nervous system will also be important in designing strategies promoting recovery of function. The investigator proposes a positional information model for cell fate determination within the zebrafish cranial neural crest. Cells in different mediolateral positions have different fates: cells located medially generate pigment cells while cells positioned laterally form neurons and glia. The investigator proposes that expression of wnt1 and wnt3a in the dorsal neural tube acts as a medial signal to promote pigment cell fates and inhibit neural cell fates. Expression of BMP2 lateral to the neural crest, and the BMP inhibitor chordin medial to the crest, sets up a lateral signal that opposes the wnt signal. The investigator will test the role of BMP in neural crest specification by injecting individual cells with mRNA encoding activators and inhibitors of BMP signaling and following their development in vivo. In his model, cells located in different positions respond to distributed signals by turning on specific transcription factors that direct the subsequent steps of differentiation. The investigator proposes that the nacre gene, initially identified in a genetic screen for neural crest regulators, acts as such a transcription factor to initiate melanogenesis at the expense of neurogenesis. To test these ideas, the investigator will determine if nacre is sufficient for melanogenesis and whether it is a direct downstream target of wnt signaling. The striking coincidence of lateral neural crest cells that produce neurons and neuron-forming placodes has led the investigator to hypothesize that these cells may be part of the same field, and may thus respond to the same mediolateral signals. The investigator proposes to test this idea by producing a detailed fate map of a putative """"""""placode field"""""""" and directly compare it to the neural crest fate map. He will test whether BMP2 plays a role in distinguishing between neural crest and placode.
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