The long-term goal of this project is a detailed understanding of the cellular and molecular mechanisms that control the development of the adult peripheral nervous system (PNS) of the fruit fly Drosophila. This system has proven to be a particularly accessible and productive setting in which to investigate fundamental problems in animal development, including pattern formation, cell fate specification, and differentiation. Cell-cell signaling via the Notch (N) receptor is a principle mechanism for assigning cell fates in a broad variety of developmental processes in metazoans, including neurogenesis. We have identified a novel family of seven genes that are not only known or likely targets of transcriptional activation by the N pathway, but also encode small proteins that are potent modulators of N signaling activity. Since these predicted proteins have in common a strongly basic amphipathic alpha-helical domain, like the product of the founding member, Bearded, we refer to this gene set as the Bearded (Brd) family. The research plan outlined in this application makes use of a combination of classical and molecular genetics, cell biology, and biochemistry to elucidate the function and regulation of this new group of genes: (1) Genetic analysis of Brd family gene function. (2) Molecular genetic analysis of Brd family transcriptional regulation. (3) Cell biological and biochemical analysis of the expression and function of Brd family proteins. By focusing on a key cell fate specification system, this research project offers the prospect of significant advances in our mechanistic understanding of development regulation at the cellular and biochemical levels.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM046993-12
Application #
6636045
Study Section
Genetics Study Section (GEN)
Program Officer
Tompkins, Laurie
Project Start
1992-02-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2005-03-31
Support Year
12
Fiscal Year
2003
Total Cost
$249,005
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Miller, Steven W; Posakony, James W (2018) Lateral inhibition: Two modes of non-autonomous negative autoregulation by neuralized. PLoS Genet 14:e1007528
Smith, Andrew F; Posakony, James W; Rebeiz, Mark (2017) Automated tools for comparative sequence analysis of genic regions using the GenePalette application. Dev Biol 429:158-164
Miller, Steven W; Rebeiz, Mark; Atanasov, Jenny E et al. (2014) Neural precursor-specific expression of multiple Drosophila genes is driven by dual enhancer modules with overlapping function. Proc Natl Acad Sci U S A 111:17194-9
Liu, Feng; Posakony, James W (2014) An enhancer composed of interlocking submodules controls transcriptional autoregulation of suppressor of hairless. Dev Cell 29:88-101
Hirono, Keiko; Margolis, Jonathan S; Posakony, James W et al. (2012) Identification of hunchback cis-regulatory DNA conferring temporal expression in neuroblasts and neurons. Gene Expr Patterns 12:11-7
Rebeiz, Mark; Castro, Brian; Liu, Feng et al. (2012) Ancestral and conserved cis-regulatory architectures in developmental control genes. Dev Biol 362:282-94
Liu, Feng; Posakony, James W (2012) Role of architecture in the function and specificity of two Notch-regulated transcriptional enhancer modules. PLoS Genet 8:e1002796
Rebeiz, Mark; Miller, Steven W; Posakony, James W (2011) Notch regulates numb: integration of conditional and autonomous cell fate specification. Development 138:215-25
Miller, Steven W; Avidor-Reiss, Tomer; Polyanovsky, Andrey et al. (2009) Complex interplay of three transcription factors in controlling the tormogen differentiation program of Drosophila mechanoreceptors. Dev Biol 329:386-99
Schweisguth, F; Nero, P; Posakony, J W (1994) The sequence similarity of the Drosophila suppressor of hairless protein to the integrase domain has no functional significance in vivo. Dev Biol 166:812-4

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