In Drosophila and similar model genetic organisms, genes playing pivotal developmental roles in embryogenesis have been identified in screens for zygotic and maternal-effect lethals. Molecular characterization of these mutated loci has been the focus of many labs' research programs over the last two decades, and consequently, the signaling events that direct patterning (e.g. DV axis determination) and morphogenetic (e.g. dorsal closure) processes have been very well characterized. Despite mutagenesis experiments that are nearly saturating, only a very few genes have been identified that fine tune the signaling process (e.g. corkscrew) and/or control the mechanics of development (e.g. concertina and folded gastrulation). Put another way, although signal transducers and transcription factors have been identified in abundance, the fine-tuners (here referred to as facilitators) and the downstream effectors of these signaling cascades have remained, in large part, unidentified and uncharacterized. The additional genes that are essential for embryonic development in Drosophila might be overlooked in genetic screens because they mutate to phenotypes affecting only one part of a complex pattern or because they do not mutate to lethality. We have exploited enhancer/suppressor and reverse genetic methods to identify Dpp signaling molecules that were missed in more traditional genetic surveys.
The specific aims of the current research application are to: (1) characterize the function of eop (enhancer of punt), a newly identified component of the DPP-mediated signaling pathway, (2) characterize the role of the spatially-restricted scylla and charybde transcripts in executing DPP-mediated signaling and dorsal differentiation during embryogenesis, and (3) conduct a high-throughput screen for additional spatially-restricted transcripts and putative effectors of DPP-mediated signal transduction. We expect that the proposed studies to provide significant insight into cellular processes regulated by Dpp-mediated signal transduction.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061972-03
Application #
6636521
Study Section
Genetics Study Section (GEN)
Program Officer
Greenberg, Judith H
Project Start
2001-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
3
Fiscal Year
2003
Total Cost
$231,000
Indirect Cost
Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Sivachenko, Anna; Gordon, Hannah B; Kimball, Suzanne S et al. (2016) Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases. Dis Model Mech 9:377-87
VanHook, Annalisa; Letsou, Anthea (2008) Head involution in Drosophila: genetic and morphogenetic connections to dorsal closure. Dev Dyn 237:28-38
Scuderi, Anne; Simin, Karl; Kazuko, Sandra G et al. (2006) scylla and charybde, homologues of the human apoptotic gene RTP801, are required for head involution in Drosophila. Dev Biol 291:110-22
Scuderi, Anne; Letsou, Anthea (2005) Amnioserosa is required for dorsal closure in Drosophila. Dev Dyn 232:791-800
Li, Xinghai; Scuderi, Anne; Letsou, Anthea et al. (2002) B56-associated protein phosphatase 2A is required for survival and protects from apoptosis in Drosophila melanogaster. Mol Cell Biol 22:3674-84
Simin, Karl; Scuderi, Anne; Reamey, James et al. (2002) Profiling patterned transcripts in Drosophila embryos. Genome Res 12:1040-7