email: grunwald@genetics.utah.edu

Professor of Human Genetics Grunwald Lab Home page Developmental Neuroscience

B.A. 1975, Williams College; Ph.D. 1981, University of Wisconsin.

RESEARCH:

Tissue specification during zebrafish embryogenesis

Animal form arises as a consequence of patterning events that occur during embryogenesis and bring about the specification of pools of tissue precursor cells. The Grunwald laboratory focuses on the factors that regulate the patterned origin of tissue precursor cells in the zebrafish embryo. We exploit strengths of the zebrafish system including the isolation and analysis of new mutations in regulatory genes required for the formation of tissue precursor populations and the use of microarray analysis of mutant embryos to discover genes that function in tissue patterning pathways.

The laboratory studies three aspects of tissue patterning in the early embryo. One focus is the role of T-box genes in establishing distinct regions of the early mesoderm. Multiple T-box genes, which encode related transcription factors, are expressed in overlapping domains that together span the entire mesoderm. Our work indicates the group of T-box genes form an interacting regulatory network, much like the HOX genes, to create regions of the mesoderm with distinct patterns of gene expression and fate. Current work focuses on the mechanisms by which the T-box factors interact to regulate downstream gene expression. A second project is aimed at identifying genes that contribute to building the anteroposterior axis of the embryo and to patterning the nervous system into distinct regions along this axis. The ichabod gene product is required in the WNT-signaling pathway that initiates axis formation and ichabod mutants are defective in axis formation. We are using microarray analysis to identify the earliest genes that fail to be expressed in ichabod mutant embryos and testing their individual roles in axis formation and neural patterning. A third project is to define the sequence of gene actions that leads to establishment of the early premigratory population of neural crest cells. Using mutants we and others have isolated, in combination with cell lineage analyses, we are identifying the signaling pathways that govern the initial induction and proliferation of the progenitor cells that give rise to the neural crest.

Selected Publications

Lamason, R.L., et al. (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and man. Science, 310:1782-1786.

Goering, L. M., Hoshijima, K., Hug, B., Bisgrove, B. W., Kispert, A., and Grunwald, D. J. (2003) An interacting network of T-box genes directs gene expression and fate in the zebrafish mesoderm. Proceedings National Academy of Sciences (USA), 100:9410-9415.

Grunwald, D. J., and Eisen, J. S. (2002) Headwaters of the zebrafish - emergence of a new model vertebrate. Nature Reviews Genetics 3:717-724.

Hoshijima, K., Metherall, J. E., and Grunwald, D. J. (2002) A protein disulfide isomerase expressed in the embryonic midline is required for left/right asymmetries. Genes & Development 16:2518-2529.

Korzh, V., and Grunwald, D. J. (2001) Nadine Dobrovolskaia-Zavadskaia and the dawn of developmental genetics. Bioessays 23:365-371.

Appel, B., Fritz, A., Westerfield, M., Grunwald, D. J., Eisen, J., and Riley, B. B. (1999) Delta-mediated specification of midline cell fates in zebrafish embryos. Curr. Biol. 9:247-256.

Cretekos, C. J., and Grunwald, D. J. (1999) alyron, an insertional mutation affecting early neural crest development in zebrafish. Develop. Biol. 210:322-338.

Dorsky, R. I., Snyder, A., Cretekos, C. J., Grunwald, D. J., Geisler, R., Haffter, P., Moon, R. T., and Raible, D. W. (1999) Maternal and embryonic expression of zebrafish lef1. Mech. of Develop. 86:147-150.

Hug, Walter, and Grunwald. (1997) tbx6, a Brachyury-related gene expressed by ventral mesendodermal precursors in the zebrafish embryo. Developmental Biology 183:61-73.

Riley, B. R., and Grunwald, D. J. (1995) Efficient induction of point mutations allowing recovery of specific locus mutations in zebrafish. PNAS 92: 5997-6001.

Helde, K. A., Wilson, E. T., Cretekos, C. J., and Grunwald, D. J. (1994) Contribution of early cells to the fate map of the zebrafish gastrula. Science 265: 517-520.

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