Project Details


The developmental biology and differentiation of higher eukaryotes require
many genes to be subject to multiple control mechanisms which regulate the
time of expression, the tissues in which it occurs, and even the physical
pattern of the cells in which the gene is active. We will approach the
molecular basis of these mechanisms using the white (w) gene of Drosophila
and its interactions. This gene, most intensively studied genetically, is
a unique system to study specificity of expression, dosage compensation:
the sex specific regulation which affects X chromosome genes and
transvection. This last phenomenon depends on the zeste (z) locus and
affects the white gene and at least two other loci, bithorax (BX-C) and
decapentaplegic (dpp), of fundamental developmental importance. We will
study these mechanisms by analyzing the effects of an array of mutants on
white gene expression, its specificity and distribution, using Northern
blots, S1 mapping, assays of w-product, and in situ detection in thin
sections from different developmental stages. We will dissect the
functions of the regulatory region using P-mediated transformation to
reintroduce altered versions of the w gene into flies. We have cloned and
will complete the analysis of the zeste gene, including the isolation of
its product. The interaction of the z-product with chromosomes and their
constituents will be explored in situ. In particular, we will look at its
interaction with the DNA of its targets in w, BX-C, and dpp loci. The mode
of action of the z-product will be analyzed also using mutations in
suppressor of zeste loci. We will then attempt to clone these loci which
suggest an involvement of zeste in vital cellular processes. The analysis
of insertional mutants in w and z will also be continued to study their
effects on transcription, termination, and splicing. The pursuit of one of
these, w-a and a second site suppressor mutation promises to lead us to the
mechanism of transcription termination.
Effective start/end date4/1/853/31/93


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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