CELLULAR COMMUNICATION IN DROSOPHILA DEVELOPMENT

Project Details

Description

My laboratory is interested in how patterns are formed in developing
organisms. In particular, we are interested in how cellular
communication contributes to developmental decisions. We previously
discovered that the decapentaplegic gene of Drosophila is a member of the
secreted transforming growth factor-beta (TGF-beta) family and is
therefore involved in cellular communication. Recently, a number of
proteins have been identified which complex with, and alter the
activities of TGF-beta members. One candidate gene from Drosophila, the
tolloid gene, encodes a protein which augments the activity of
decapentaplegic. This proposal is aimed at determining the developmental
role and the mechanism by which tolloid contributes to the development
of Drosophila, focusing on its interaction with the decapentaplegic gene.
Both these genes are involved in establishing dorsal-ventral cell fates
in the dorsal ectoderm. Several lines of genetic and molecular evidence
link the activity of tolloid and decapentaplegic. In particular, the two
vertebrate homologs of these genes, bone morphogenetic protein-1 (BMP1)
and bone morphogenetic protein-4 (BMP4) copurify with each other,
suggesting their interactions are at the protein level. Recent molecular data indicates that the tolloid gene is duplicated in
tandem in the 96A region of the Drosophila chromosome. The tolloid
related-1 (tldr-1) gene lies between a P element, where our molecular
walk began, and tolloid, which is about 30 kb from the P element. Both
these genes contain a protease domain, EGF repeats and the repeats found
in the blood complement genes, Clr and Cls. Presently, there are only
a few genes implicated in pattern formation which encode proteases, and
this study should provide general insights into how they regulate cell
growth. To study the tolloid-like genes in Drosophila, we plan to: 1)
characterize their expression in embryos and larval tissues in detail,
2) generate mutations in the tldr-1 gene to aid in determining its role
during development, 3) dissect structure-function aspects of the tolloid
gene by sequencing mutant alleles and generating in vitro mutations for
reintroduction into the fly, 4) express tolloid and decapentaplegic in
cell lines to biochemically characterize their interaction by
immunoprecipitation and to characterize the protease activity of the
tolloid protein. Since the expression pattern of tolloid and tldr-1
includes larval and pupal stages, they may interact with decapentaplegic
at later times of development. We already have a putative point mutation
in the tldr-1 gene. These experiments will provide insight into the
action and mechanism of this interesting growth factor in Drosophila and
contribute to a general understanding of the role of proteases in pattern
formation and cellular communication in animals.
StatusFinished
Effective start/end date1/1/9312/31/03

Funding

  • National Institutes of Health: $212,694.00
  • National Institutes of Health: $153,727.00
  • National Institutes of Health: $207,047.00
  • National Institutes of Health: $199,894.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $141,649.00
  • National Institutes of Health
  • National Institutes of Health

ASJC

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

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