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 early pattern formation in several ways. This laboratory and others have shown previously that the Wnt signaling cascade regulates the initial dorsoventral polarization in the embryo. The relationships between Wnt factors and certain Frizzled proteins, recently identified as Wnt receptors, have been studied, leading to the conclusion that Frizzled 5 could act as a receptor for Wnt-5A. Further, Wnt factors were shown to have a role in the patterning of the early CNS. Wnt-3a and Wnt-1, but not the related factor Wnt-8, are capable of modifying the specification of neural tissue to a more dorsal fate. In particular, Wnt-3a and Wnt-1 induce neural crest differentiation in ectoderm that has been neuralized by the action of noggin. Members of the TGF-beta superfamily are involved in early embryogenesis in the induction and patterning of mesoderm and ectoderm. Among these factors, members of the nodal subfamily are of particular interest. Two nodal-related (ndr) genes from the zebrafish were isolated and their expression and function in the embryo was studied. Both nrd-1 and ndr-2 are expressed in the shield (organizer) of the zebrafish embryo, but they occupy non-overlapping regions indicating that the shield is organized into different transcriptional domains. Ndr-1 and Ndr-2 are capable of dorsalizing the embryo and inducing neural markers, and their overexpression caused duplication of the trunk axis in zebrafish embryos. 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. Experiments have been initiated to study Xlim-1 function with the use of constructs that contain the Xlim-1 DNA binding domain and the repressor domain of engrailed. A role of Xlim-1 in head formation is suggested by the results, as also demonstrated in the mouse by another research group. The engrailed repressor domain technique is a promising approach to study the developmental function of transcription factors in development.
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