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.
