In this proposal we describe experiments to extend our previous analysis of the scratch (scrt) gene which encodes a pan-neural transcription factor likely to function as a repressor of non-neuronal gene expression (Specific Aim l). We also propose to follow a new line of investigation focused on the analysis of the short gastrulation (sog) gene, which we isolated in the course of our studies of pan-neural enhancer elements. sog is expressed in the early neuroectoderm and encodes likely antagonist of the TGFbeta-like Dpp signaling pathway (Specific Aims II-IV). Sog and the Dpp signaling pathway have been highly conserved during evolution. Dpp and its vertebrate homologue BMP-4 can functionally substitute for each other in dorsalventral pattern formation in flies and in bone morphogenesis in vertebrates. In addition, a Xenopus homologue of sog known as chordin has been identified recently. Like sog and dpp in flies, chordin and BMP-4 also have opposing effects on dorsal-ventral patternIng. Thus, it is likely that the sog,/chordin and dpp/BMP-4 genes play conserved roles in early dorsal-ventral patterning in invertebrates and vertebrates. These studies are therefore highly relevant to understanding the regulation of growth factors in the TGFbeta superfamily. Specific research goals are to: I. Determine how the pan-neural genes scratch and deadpan collaborate to promote neurogenesis. II. Determine whether sog is a dedicated inhibitor of Dpp signaling in flies and frogs. III. Identify enhancer element(s) directing sog expression during embryonic and adult development. IV. Determine whether a Sog protein(s) is secreted, diffuses, and binds to Dpp.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029870-08
Application #
2883653
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Finkelstein, Robert
Project Start
1992-05-01
Project End
2001-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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