This laboratory has studied the molecular basis of embryogenesis in Xenopus laevis and the zebrafish, with special emphasis on axis determination and pattern formation. These events are thought to be controlled by cell-to-cell signaling and by the spatially and temporally regulated action of transcription factors. The Wnt family of signaling molecules is involved in development in many ways. An important component of Wnt signaling is the interaction between Wnt factors and soluble antagonists which can modulate the signal. In collaboration with the laboratory of Jeremy Nathans at John Hopkins University, a novel Wnt-binding factor, named WIF-1, has been characterized previously. To determine the biological properties of WIF-1, a targeted deletion of this gene is being generated in the mouse in collaboration with Heiner Westphal's group. The Xlim-1 gene encodes a LIM-homeodomain protein that has been shown to be involved in the functions of the Spemann organizer in neural induction and mesoderm patterning. This gene is also important in kidney formation, a function that is being studied by different intervention strategies such as negative interfering constructs and antisense strategies.A screen for developmentally regulated genes is being conducted in zebrafish. Two genes, vega1 and vega2, that were characterized recently are critical for the earliest transcriptional regulation of dorsal-ventral polarity in the embryo. A distinct gene has been studied that modulates signaling by the BMP (bone morphogenetic protein) pathway, which has a major role in patterning the gastrula embryo. In addition, a genetic screen has been initiated that uses a chemical mutagen expected to generate deletions in the zebrafish genome. Such lesions are expected to be very useful in the genetic and functional characterization of zebrafish genes.
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