This proposal deals with Drosophila melanogaster as a model system in molecular endocrinology, and more specifically with a gene that encodes the Drosophila homolog to the mammalian H2RII binding protein. Both are members of the steroid hormone receptor gene superfamily. The mammalian protein participates in the transcriptional regulation of the major histocompatibility complex (MHC) class I genes which, in turn, plays a central role in T-cell lymphocyte recognition of certain carcinomas. Studies suggest that H2RII binding protein also plays a currently unexplored role in some aspect of neural regulation and may modify the transcriptional regulation of the estrogen receptor. The proposed experiments will exploit the numerous technical attributes of Drosophila melanogaster, primarily the wealth of genetic information, to investigate the role of this receptor-like gene product in development. The gene maps to the distal portion of the X chromosome (cytological position: 2C) and is expressed during embryogenesis.
The specific aims are: (1) to examine the expression of the 2C gene through development; (2) to obtain a physical map of the 2C gene locus; (3) to identify genes transcriptionally regulated by the 2C gene product; (4) to isolate and characterize mutations of the 2C gene and mutations of loci which interact with the 2C gene product; (5) to test the 2C gene product for its cognate ligand (e.g. ecdysteroid, juvenile hormones, retinoic acid, etc.) and (6) to characterize other candidate receptor clones isolated in our initial genomic screen. The results of these experiments should provide significant insights concerning the role of endocrine factors in mediating the orderly progression of development in Drosophila and perhaps other eukaryotic organisms. More generally, these findings will lead to specific lines of investigation concerning the regulatory role of the H2RII binding protein in mammalian systems.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR006627-04
Application #
3421644
Study Section
Special Emphasis Panel (SRC (BM))
Project Start
1990-09-30
Project End
1995-09-29
Budget Start
1993-09-30
Budget End
1994-09-29
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Arts and Sciences
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Henrich, V C (1995) Comparison of ecdysteroid production in Drosophila and Manduca: pharmacology and cross-species neural reactivity. Arch Insect Biochem Physiol 30:239-54
Song, Q; Gilbert, L I (1995) Multiple phosphorylation of ribosomal protein S6 and specific protein synthesis are required for prothoracicotropic hormone-stimulated ecdysteroid biosynthesis in the prothoracic glands of Manduca sexta. Insect Biochem Mol Biol 25:591-602
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Dai, J D; Henrich, V C; Gilbert, L I (1991) An ultrastructural analysis of the ecdysoneless (l(3)ecd1ts) ring gland during the third larval instar of Drosophila melanogaster. Cell Tissue Res 265:435-45