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Return to: College of Biological Sciences: Medical School: U of M Home |
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Areas of Research Strength: Early vertebrate neural development molecular embryology back to top |
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Research Techniques: mouse and chick embryology
in ovo electroporation
mouse genetics
in situ hybridization
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Research Interests: The neural crest. Early development requires many highly orchestrated, directed cell movements. One of the most striking examples of this is the vertebrate neural crest. Neural crest cells arise in the developing central nervous system, but become disconnected from their neighbors and migrate over long distances throughout the embryo to form surprisingly diverse derivatives including the peripheral nervous system, outflow tract of the heart, and craniofacial skeleton. The importance of these events is clear: abnormalities in neural crest development lead to a variety of common birth defects (such as cleft lip/palate) and cancers (such as melanoma and neuroblastoma). To tackle these health issues, we must first establish the basics. How do neural crest cells become different from their neighbors and migrate? How do they know where to go? How do they maintain their stem cell-like multipotency? The goal of research in the Gammill laboratory is to elucidate the molecular mechanisms regulating neural crest formation, migration, and guidance. A combinatorial approach to studying early neural crest development. Drawing on a gene expression profile of a newly induced neural crest cell, the Gammill lab is characterizing early neural crest regulators in chick and mouse embryos using a variety of approaches. These include manipulating chick embryos by injection (dyes or cells), graft (tissues or beads), or electroporation (DNA or oligonucleotides), culturing chick and mouse embryonic tissue explants, and creating and analyzing mouse mutants. This combination of organisms and techniques allows us to exploit the advantages of each system toward a clearer understanding of early neural crest development. A neural crest guidance cue. One example of this approach is the lab's work with the receptor neuropilin 2 (npn2). Neural crest cells migrate along stereotypical pathways in a pattern that prefigures the arrangement of the structures they form, such as the ganglia of the peripheral nervous system. However, the signals that direct this patterned migration were not understood. The lab's experiments in chick demonstrated that neural crest cells express npn2, and by characterizing mice mutant for npn2 and its repulsive ligand semaphorin 3F, we showed that signaling between npn2 on neural crest cells and sema3F in the environment is required to guide neural crest migration. With a neural crest guidance molecule in hand, they are now looking at signals downstream of npn2 that impact the subsequent pattern of neural crest differentiation, and using a similar methodology to characterize additional neural crest candidate regulatory molecules. back to top |
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Selected Publications: Gammill, L.S., Gonzalez, C., Bronner-Fraser, M. (2007). Neuropilin 2/semaphorin 3F signaling is essential for cranial neural crest migration and trigeminal ganglion condensation. Dev. Neurobiol., 67(1): 47-56. Gammill, L.S., Gonzalez, C., Gu, C., Bronner-Fraser, M. (2006). Guidance of trunk neural crest migration requires neuropilin 2/semaphorin 3F signaling. Development, 133, 99-106. Coles, E.G., Gammill, L.S., Miner, J.H., Bronner-Fraser, M. (2006). Abnormalities in neural crest migration in laminin a5 mutant mice. Dev. Biol., 289, 218-228. Gammill, L.S. and Bronner-Fraser, M. (2003). Neural crest specification: migrating into genomics. Nat Rev Neurosci., 4(10):795-805. Gammill, L.S. and Bronner-Fraser, M. (2002). Genomic analysis of neural crest induction. Development, 129, 5731-5741. To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed search menu should say PubMed type Gammill LS in the avaliable line back to top |
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