BIOCHEMISTRY OF EARLY MAMMALIAN DEVELOPMENT

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Two genetic abnormalities affecting mammalian embryonic development will be investigated. Oligosyndactyly (Os) and dominant yellow (Ay) are both mutations which in the heterozygous form cause developmental abnormalities and in the homozygous form cause early embryonic death. Since the Ay mutation appears to be associated with the insertion of an ecotropic virus, the molecular basis of this mutation will be studied using probes to be developed against the Ay-associated proviral integration site and flanking host DNA sequences. The normal mRNA transcripts of the agouti locus will be identified in early embryos and the effects of the mutation assessed. Ay/Ay teratocarcinoma cell lines will be prepared and Ay/Ay equal to +/+ chimeras analyzed. Studies to correct the defect in Ay/Ay cells and to reproduce the defect in +/+ cells will be undertaken by microinjection of cloned DNA. The effect of dibutyryl cAMP on the ability of Ay/Ay embryos to hatch in vitro will be assessed. The relationship between the heterozygous manifestations of Os and the mitotic defect identified in Os/Os embryos will be analyzed. Cellular proliferation in Os/+ egg cylinders and limb buds will be determined, and the effect of the calcium ionophone, A23187, assessed.