This laboratory has studied molecular basis of embryogenesis in the Xenopus laevis and the zebrafish, with special emphasis on early pattern formation and axis determination. 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 early pattern formation in several ways. We have shown previously that the Wnt signaling cascade regulates the initial dorsoventral polarization in the embryo. During the past year we have studied relationships between different Wnt factors and certain Frizzled proteins, recently identified as Wnt receptors. Further, we analyzed Wnt factor function in neural patterning. Various studies have shown that the initial neuralizing signal leads to the formation of anterior structures; the mechannism of conversion to more posterior cell types is thus an important question. Other workers have suggested that certain Wnt factors have a role in posteriorization. Our recent work has made two main points. (i) In contrast to what was previously believed, there is no equivalence of function between the Wnt family members Wnt3a and Wnt8; while the former effectively converts anterior neural tissue to more posterior tissue, the latter does not. (ii) Beyond its ability to effect posteriorization Wnt3a specifically induces the neural crest. The second focus of our studies is the function of the LIM class homeodomain protein Xlim-1 in the Spemann organizer region of the gastrula embryo. We have implicated Xlim-1 in neural and muscle induction, and have shown that an activated form of Xlim-1 can stimulate the transcription of the homeobox gene goosecoid (gsc). More recently we have studied the mechanism of regulation of gsc by Xlim-1. We suggest that the gsc gene is maintained in an inactive state by a repressor. While mutated Xlim-1 protein is an activator of gsc, the wild type protein cannot act by itself but is effective in combination with Otx2. The homeodomain protein Otx2 appears capable of displacing the repressor, allowing the wild type Xlim-1 to activate the gsc gene. These studies begin to illuminate the regulatory interactions that lead to the patterning of the gastrula embryo.
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