The overall goal of the proposed research is investigation of the potential roles of proto-oncogenes in mammalian gametogenesis and early embryonic development. The c-mos c-abi and int-1 proto-oncogenes are transcribed during specific stages of spermatogenesis in the mouse. In addition, c-mos is transcribed in growing oocytes and high levels of c- mos RNA are accumulated by the germinal vesicle stage. The oocyte c-mos RNA is post-transcriptionally polyadenylated in concert with oocyte maturation and is degraded by the mid to late two cell stage, suggesting possible roles for c-mos as a maternal message. Since c-mos represents the first candidate for a regulatory maternal RNA unique to oocytes, further studies with its expression in spermatogenesis. Synthesis, phosphorylation and stability of the c-mos protein will be studied in spermatocytes, oocytes, eggs and embryos. The biological functions of c- mos in oocytes will be investigated by inhibiting c-mos expression using anti-sense oligonucleotides and/or anti-mos antibodies. These studies will be correlated with alterations in protein phosphorylation to identify candidate targets for c-mos protein kinase activity. Regulatory sequences and trans-acting factors which control c-mos expression during maturation of spermatocytes and oocytes will be investigated and the developmental specificity of c-mos expression in spermatogenesis will be further studied. The expression of additional selected proto-oncogenes will be studied in spermatogenesis, oogenesis and pre-implantation mouse embryos. These studies of normal proto-oncogene function in development will also contribute to understanding the mechanisms by which oncogenes induce neoplastic transformation.
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