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James Weston Professor, Department of Biology B.A., 1958, Cornell University Ph.D., 1963, Yale University Research Interests Cellular and genetic analysis of neural crest development; segregation of neuronal and non-neuronal lineages from neural crest-derived cells; role of specific receptor tyrosine kinases and their ligands in regulating neural crest cell behavior Email

Dr. Weston has retired from research. He continues to teach, and remains a presence at the Institute.

We are using the neural crest to learn how phenotypic differences arise and become stabilized in cell lineages of multicellular embryos. Neural crest cells emerge from the dorsal neural epithelium of vertebrate embryos and localize in an interstitial "migration staging area" (MSA). In the embryonic trunk, crest cells disperse from the MSA on two spatially and temporally distinct migration pathways (Weston, 1991). We have shown that premigratory or early migrating crest cell populations initially contain fate-restricted neurogenic and non-neurogenic subpopulations (Henion and Weston, 1997), and that at least some of these developmentally distinct subpopulations differentially express receptor tyrosine kinases whose function is required for their further development. Using a number of mouse mutations, for example, we have shown that crest-derived melanocyte precursors, but not neurogenic cells, express the receptor, c-kit, and transiently depend for survival on its ligand, stem cell factor (SCF) (Morrison-Graham and Weston, 1993; Wehrle-Haller et al., 1996). We have also shown that, in the mouse, SCF activity is differentially localized on a lateral crest migration pathway, and is required for crest-derived melanocyte precursors to disperse on that pathway (Wehrle-Haller and Weston, 1995). Likewise, we have identified subpopulations of crest-derived neurogenic cells that respond differentially to environmental cues such as retinoids (Henion and Weston, 1994) and neurotrophin 3 (NT3; Henion et al., 1995) present on the ventro-medial migration pathway in avian embryos.  We have also screened for mutations that affect the development of crest-derived neurons in the zebrafish Danio rerio  (Henion et al., 1996). We are using some of these mutant fish and other mutant resources in mice to test the hypothesis that differentially localized growth factor activities provide tropic cues to crest-derived subpopulations expressing cognate receptors, thereby causing such cells to disperse selectively on specific migration pathways (Wehrle-Haller and Weston, 1997).

Finally, we have learned that, very early in their development, neurogenic cells of vertebrate embryos express RNA-binding proteins (the Hu proteins, a.k.a "elr" proteins) homologous to the ELAV protein in Drosophila  (Marusich et al., 1994), and we have begun to characterize the mechanisms by which this protein might regulate the differentiation of neuronal cells (Wakamatsu and Weston, 1997).

Representative Publications