In multicellular
organisms, cell-cell communication involving secreted factors is an
essential means by which cells influence the fates of neighboring
cells. Members of the transforming growth factor-ß (TGF-ß) superfamily
play a key role in organizing the body axis during embryogenesis in
flies, frogs and mammals. We are interested in understanding the role
of two TGF-ß related genes, screw (scw) and decapentaplegic (dpp),
in specifying cell fate during embryonic development in the fruitfly
Drosophila. Since the TGF-ß signaling pathway is evolutionarily conserved,
findings from a genetically tractable organisms like Drosophila can
provide insights into the mechanism of action of TGF-ß proteins in
other organisms, including humans. We have cloned the scw gene and
shown that although scw transcripts are ubiquitously expressed, the
protein is only required in dorsal cells. It is likely that Scw may
be activated in a subset of the cells where it is expressed because
of its interaction with other genes involved in patterning the embryo.
We are using molecular genetic tools and biochemical techniques to
test how Scw activity is modulated post-translationally.
Another focus
in the lab is to understand the mechanism of TGF-ß signal transduction.
Despite significant progress in identifying the receptors that bind
TGF-ß ligands, the mechanism by which cells transduce these signals
and their cellular responses, have not been defined in any system.
We have recently identified the schnurri (shn) gene as an early nuclear
target in the Dpp/TGF-ß signaling pathway. Shn resembles a family
of mammalian transcription factors, and is homologous to the human
major histocompatibility binding proteins, MBP-1 and MBP-2. Our data
indicate that shn activity rather than its transcription, is regulated
by Dpp. Future experiments will center on understanding how Shn is
activated in response to Dpp.
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