The long-term objective of the research program described in this proposal is an understanding of the genetic circuitry and cellular mechanisms that control the development of the adult peripheral nervous system (PNS) of Drosophila. The basic experimental approach is to investigate the action of specific genes and gene products required for normal sensory organ patterning and/or cytodifferentiation. The proposal concerns the genes Hairless and Bearded. Loss-of-function mutations of Hairless cause the failure of sensory organ precursor cell development. Bearded mutations appear to interfere with two successive inhibitory cell-cell interaction events during sensory organ development. Using techniques of classical and molecular genetics, cell biology, and biochemistry, we propose to analyze these genes, their products, and their functions, and to identify and study new interacting genes that act in the control of PNS development. The project has the following specific aims: (1) Molecular characterization of the Hairless gene and its RNA and protein products and analysis of their spatial and temporal patterns of expression. (2) Completion of the analysis of the Hairless null developmental defect. (3) Identification and genetic/developmental analysis of loci interacting with Hairless. (4) Molecular analysis of the Bearded gene and its patterns of expression, and biochemical studies of the interaction of the Bearded protein with calmodulin. (5) Identification and genetic/developmental analysis of loci interacting with Bearded loss- and gain-of-function alleles.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM046993-01
Application #
3306523
Study Section
Genetics Study Section (GEN)
Project Start
1992-02-01
Project End
1996-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
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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