The studies described here continue and extend our research in the area of somatic cell genetics. We shall continue to refine gene mapping procedures, especially to increase the resolution of the physical map by gene transfer. A new aspect of our research will be the analysis of the molecular mechanisms of growth and differentiation. Using somatic cell genetic approaches, we have cloned genes tht are regulated in respect to the resting or proliferating states of cells. These are thymidine kinase, transferrin receptor, surface antigen 4F2, and surface antigen S11. The genes are being characterized structurally and in terms of their kinetics of transcriptional expression during the culture cycle and the cell cycle. We propose to determine the molecular mechanisms of transcriptional control in this gene set. Another new research program involves mouse and human DNA sequences that show a high degree of homology with the Drosophila homeotic genes Antennapedia and Ultrabithorax. We have cloned a number of such sequences and propose experiments by which their biological significance can be evaluated. If our hypothesis is correct that these genes regulate pattern formation in mammals, then we shall have a genetic approach to studying mechanisms of morphogenesis in higher organisms. In another new system (sr = segregation regulation), we shall investigate genetic factors located on the mammalian X chromosome that control chromosome segregation in hybrid cells. We postulate that this system represents a hitherto unrecognized mechanism that mediates intercellular recognition in somatic cell populations. A primary objective will be the purification and recombinant DNA cloning of these sr genes. We believe the pursuit of these projects will provide useful and significant insights into the genetic mechanisms controlling mammalian cell growth, differentiation, and morphogenesis.
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