The myosin heavy chain (MHC) gene of Drosophila is an excellent model system for investigating a gene whose transcription is complex and developmentally regulated. The MHC gene of Drosophila is single copy, however, three largely overlapping mature mRNAs are transcribed from the gene which differ in length. The relative expression of these transcripts is developmentally regulated. We have strong evidence that the main differences between the transcripts are due to developmentally regulated alternative splicing at the 3 feet end of the transcripts. We have preliminary evidence that the three mRNAs are translated into polypeptides which differ in their carboxy terminal amino acids. I propose to investigate the molecular basis and biological significance of this unusual developmentally regulated splicing of the Drosophila MHC gene transcripts. The proposed research is significant in several ways. First, the mechanisms involved in the developmental expression and/or alternate splicing of transcripts from a single copy gene are not know. An investigation of the Drosophila MHC gene may provide information on how these processes are regulated. The availability of a DNA mediated transformation system for Drosophila will enable us to detect sequences necessary for transcription initiation and alternate splicing. An elucidation of the molecular basis of these mechanisms in Drosophila will make a significant contribution to our understanding of gene expression in general. Second, we will determine if the transcription of the Drosophila MHC gene is tissue or organ specific and if the alternate splicing results in the synthesis of diverse MHC polypeptides. The developmental pattern of expression of the MHC mRNAs and preliminary sequencing data suggest that these mRNAs can encode different polypeptides with primary sequences similar to vertebrate MHC polypeptides. Thus a continued investigation of the Drosophila MHC gene and polypeptides will enhance our understanding of the complex processes involved in the expression of MHC genes in higher organisms. Finally, several recent investigations have described classes of EMS induced mutations in Drosophila which are unable to fly. Several of these mutations map near the MHC locus. The mutants appear normal during larval and pupal stages, can walk and jump as adults, however, they are unable to fly. An analysis of such mutations will contribute to our understanding of the molecular basis of muscle function and ultimately contribute to an understanding of muscle disease.