Laboratory of Molecular Genetics
Program in Genomics of Differentiation
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Building 6B, Room 422
The molecular basis of vertebrate embryogenesis in the zebrafish Danio rerio and the amphibian Xenopus laevis is the focus of the research in this group. As a broad approach to this question a screen for genes expressed in differential patterns during embryogenesis has been carried out in the zebrafish. Over 300 of these clones were considered suitable for further study by partial sequence analysis and radiation hybrid mapping. Information on these genes is available on ZFIN and the laboratory web site. To help develop tools for molecular-genetic analysis of zebrafish development this laboratory collaborated with others on the establishment and refinement of a radiation hybrid map for this organism. A mapping tool is available on the laboratory web site.
Mutants affecting the development of the brain are being studied, showing in one example that ribosome biogenesis is essential for this process during the first 24 hr of embryogenesis. The role of several genes in early development has been studied. These include nodal-related factors, the vega1, 2 (vent, vox) homeobox genes, and gadd45 that is involved in somitogenesis. The Nma protein has been shown to be a feedback inhibitor of BMP signaling, while Wif1 is a Wnt binding protein that can inhibit the activity of several Wnt proteins. Much attention has been focused on factors modulating FGF signaling; Sef, a novel protein, and Mkp3, a MAP kinase phosphatase, were shown to modulate Fgf signaling in the early embryo. A long-standing interest in this laboratory concerns the role of the LIM-homeobox gene Lim1 which is being studied in Xenopus. Lim1 function requires interaction with a binding molecule, named Ldb, whose properties have also been studied. Lim1 is expressed in the organizer where it has a major role in controlling gastrulation movements through its activation of the adhesion molecule PAPC.
The application of DNA microarray technology is being explored in both the Xenopus and zebrafish systems. RNA expression profiles in explants dissected from the embryo and after manipulation of different signaling pathways are being generated.