MOLECULAR REGULATION OF EARLY XENOPUS DEVELOPMENT

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Development of the vertebrate embryo is dependent on a process termed induction in which intercellular communication is utilized to specify the precise organization of the cells comprising the embryonic body plan. Two growth factors have been recently identified as likely regulators of these inductive events. This proposal focuses specifically on the role of one of these, basic fibroblast growth factor (bFGF), as it both induces the formation of mesodermal cell types and is present in the early embryo. Three aspects of bFGF-mediated mesoderm induction will be pursued. 1. In order to determine how mesoderm is patterned in a restricted region of the early embryo, the bFGF protein will be localized. As mesoderm induction may instead be controlled by the regulated secretion of bFGF, the release of bFGF from the early blastomeres will be studied. Finally, the function of bFGF in the embryo will be inhibited in order to define its in vivo role in the inductive process. 2. The novel finding that the oocyte contains an anti-sense mRNA that causes the covalent modification of the bFGF transcript will be further investigated to determine whether this modification is part of a mechanism of targeted degradation of the bFGF transcript. In addition, the protein encoded by the anti-sense transcript will be extensively characterized. 3. As little is known about the cellular response to bFGF during the induction of mesoderm, cDNA copies of the RNAs expressed in response to bFGF will be isolated. Genes that are transcribed early in the inductive process or in a particular part of the mesoderm will be studied initially, with a long range goal of defining the hierarchy of genetic changes initiated by bFGF. As birth defects arise from a failure in the mechanisms of embryogenesis, it is important to understand the normal pathway of development. Since bFGF s not only involved in development regulation but can also convert common issues in different medical fields.