GENETIC AND HORMONAL CONTROL OF NEURAL REORGANIZATION

Project: Research project

Project Details

Description

The versatile experimental organism Drosophila melanogaster is
presented as a model system in which to study the role of steroid
hormones and gene expression in nervous system reorganization
during metamorphosis. In the nervous systems of both vertebrates
and invertebrates, the action of steroid hormones results in
neurogenesis, cell death, and/or changes in neuronal structure.
In general, steroid hormones are believed to exert their effects
by altering gene expression at the transcriptional level. Thus,
it is hypothesized that the steroid molting hormone ecdysterone
orchestrates Drosophila CNS metamorphosis and that it does so
primarily by modifying gene expression in the nervous system. The
proposed experiments to test this hypothesis include classical
(mutational) and molecular genetic (gene cloning) approaches, and
make use of both standard histological and as well as modern
immunohistochemical techniques. Initially, the maturation of the Drosophila CNS during
metamorphosis will be described at the light microscopic level,
yielding a staging system which will be used in subsequent analyses
of mutants and in vitro CNS development. The dependence of CNS
metamorphosis on ecdysterone will be determined by examining the
CNS in animals which are ecdysterone-deficient an by culturing the
CNS with and without the hormone. Next, the role of a known
ecdysterone-inducible regulatory locus will be evaluated by
examining the CNS in mutants and genetic mosaics, and by a direct
search for ecdysterone-induced transcripts using cloned probes from
this locus. An in vivo culture system peculiar to insects is
proposed and will be tested as a novel screening method for
developmental mutants likely to be required in the CNS for its
normal maturation during metamorphosis. Finally, a scheme is
outlined for isolating genes regulated by ecdysterone in the CNS.
Genomic and cDNA libraries will be screened by differential- and
subtraction-hybridization methods in order to isolate genes which
are repressed or induced by the hormone. One of the hormone-
inducible genes will be characterized in detail, by determining its
developmental and tissue specificity and by DNA sequence analysis. A compete understanding of human neurological disorders, especially
those with hereditary bases, will ultimately require the
elucidation of basic cellular and molecular mechanisms of neural
development. By using the sophisticated genetics of a simple
insect to unravel naturally occurring, hormone-mediated nervous
system reorganization, insights into human neurological disorders
may emerge.
StatusFinished
Effective start/end date2/1/881/31/93

Funding

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

ASJC

  • Medicine(all)
  • Neuroscience(all)

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