PROTEIN/NUCLEIC ACID INTERACTIONS IN VERTEBRATE EMBRYOGENESIS

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In vertebrates, as in other animals, the ectoderm has two primary fates, epidermis and central nervous system (CNS). The goal of this project is to understand the mechanisms that determine how ectodermal cells choose between these two pathways, and how the ensuing tissue patterning and differentiation are regulated. The main focus of the laboratory has been on the function of a homeodomain gene, Distal-less-3 (Dlx3), in these processes. Dlx3 is expressed in the ectoderm beginning at the early gastrula stage. By the neural tube stage Dlx3 expression is predominantly limited to the epidermis where it continues to be transcribed throughout the life of the animal. However, during early to mid- gastrulation, when the initial patterning of the neuroectoderm is taking place, the Dlx3 gene is transiently expressed in the anterior region of the future neural plate. This expression is significant because Dlx3 can act as a negative regulator of a subset of neural-specific genes, including that are important in the control of early CNS differentiation. The gastrula- stage expression domain of Dlx3 overlaps partially with that of another antineural homeodomain gene, Msx1, with Dlx3 transcription extending more posteriorly than that of Msx1. We have also found that Msx1 selectively blocks a subset of neural-specific genes, in a pattern complementary to that of Dlx3, and that Msx1 and Dlx3 exhibit differential sensitivity to inducer molecules (BMPs) that are thought to regulate tissue identity in the developing ectoderm. We conclude that these two transcription factors collaborate to translate one or more embryonic dorsalizing signals into an initial spatial pattern of the anterior neural plate. In the coming year, the lab will focus on identifying other regulators of epidermis, partly by investigating genes that have previously been reported to have pro-epidermal function, and also by carrying out a subtractive and DNA sequence analysis screen to identify novel factors with this property. We will also carry out experiments aimed at elucidating the mechanism by which Dlx3 can inhibit neural development. - epidermis, Xenopus laevis, neural development, Distal-less, Dlx3, Msx1