How do cells within the growing nervous system acquire the specific characteristics necessary for them to carryout their proper function in the appropriate location? This fundamental question of neurobiology is not only important in understanding the proper construction of a structure as complex as the nervous system, but is critical for understanding what goes awry from birth defects, or what happens when cells lose growth control in cancer. Understanding the events leading to formation of a functioning nervous system will also be important in design of strategies for recovery of function in treating disease. The investigator has been studying how the peripheral nervous system is generated by the neural crest. The long-term goal is to learn how neural crest cells make decisions about which types of derivatives they will form. They plan to address this issue in zebrafish, a vertebrate with distinct advantage for embryological and genetic study. They have proposed a model where interactions among neural crest cells influence their subsequent fates, in a manner reminiscent of lateral specification interactions in fly and nematode equivalence groups. They will test this idea in the zebrafish head, where cranial crest cells in spatially distinct locations have specific fates. Specifically, they will test the hypothesis that cranial neural crest cells in specific locations are restricted in developmental potential. Using the well-defined fate map of the cranial neural crest, They will transplant individual cells to different locations and determine whether they alter their fate according to their new environment. They will also test the idea that interactions among cranial neural crest cells influence their neurogenic ability. They will ablate the neural crest cells that generate the trigeminal ganglion and determine whether they are functionally replaced by cells normally destined to generate other derivatives. They will also determine whether molecules that play a role in lateral specification in invertebrate equivalence groups are specifically expressed in cranial neural crest cells. They will determine which steps in cranial crest development are affected in laughing man, a mutation that disrupts the formation of the cranial ganglia, and will screen for new mutations affecting development of cranial ganglia. These fresh approaches should provide new insight into neural crest cell fate specification.
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