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XENOPUS NOTCH AND NEURAL DETERMINATION

$248,042P01FY2000NSNIH

Salk Institute For Biological Studies, La Jolla CA

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Abstract

The formation of the vertebrate embryo begins in early development when one portion of the embryo, the ectoderm, is divided into neural and epidermal tissue on the basis of determinative cell-cell interactions. These events underlie the formation of the neural plate and tube, a process in which abnormalities during human development lead to syndromes such as neural tube defects, of which spina bifida is a well known example. These events have been difficult to study, however, because the molecules necessary for acquiring the neural fate in vertebrate embryos are unknown. To overcome this problem, an approach was taken based on the genetic analysis of neural development in Drosophila, where the product of the Notch gene appears to be a critical cell surface receptor mediating determinative cell-cell interactions. A frog homolog of this gene was isolated, suggesting that Notch-mediated, cell-cell interactions may also occur during early neurogenesis in vertebrates. The role of Notch will be studied by generating frog embryos that are mutant for the Notch protein. Moreover, Notch function will be further dissected by isolating ligands for the frog Notch receptor. The functional characterization of Notch and its ligands should lead to a better understanding of the mechanisms underlying the specification of neural tissue in vertebrate embryos.

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