This proposal seeks to understand how regulatory genes control CNS development. Specifically, it explores the regulation and function of the single-minded gene, which controls the formation of a group of neurons and glia that lie along the midline of the Drosophila CNS. Genes that control dorsal-ventral patterning activate single-minded transcription specifically in the midline precursor cells. single-minded then activates transcription of a large group of genes that carry-out the CNS midline lineage developmental program. Sequence analysis indicates that single-minded belongs to the basic-helix-loop-helix family of transcription factors, which includes regulators of nervous system and muscle development as well as growth control, carcinogen metabolism, and sex determination. In this grant, we will investigate how single-minded controls midline gene expression at the biochemical level. Additionally, the role of genes shown by genetics to influence single-minded transcription will be investigated using biochemistry and germline transformation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025251-08
Application #
2199462
Study Section
Neurology C Study Section (NEUC)
Project Start
1993-10-01
Project End
1997-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Biochemistry
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Crews, Stephen T (2010) Axon-glial interactions at the Drosophila CNS midline. Cell Adh Migr 4:67-71
Mitchell, Brian; Crews, Stephen T (2002) Expression of the Artemia trachealess gene in the salt gland and epipod. Evol Dev 4:344-53
Hu, S; Sonnenfeld, M; Stahl, S et al. (1998) Midline Fasciclin: a Drosophila Fasciclin-I-related membrane protein localized to the CNS midline cells and trachea. J Neurobiol 35:77-93
Nambu, J R; Chen, W; Hu, S et al. (1996) The Drosophila melanogaster similar bHLH-PAS gene encodes a protein related to human hypoxia-inducible factor 1 alpha and Drosophila single-minded. Gene 172:249-54
Hu, S; Fambrough, D; Atashi, J R et al. (1995) The Drosophila abrupt gene encodes a BTB-zinc finger regulatory protein that controls the specificity of neuromuscular connections. Genes Dev 9:2936-48
Franks, R G; Crews, S T (1994) Transcriptional activation domains of the single-minded bHLH protein are required for CNS midline cell development. Mech Dev 45:269-77
Lewis, J O; Crews, S T (1994) Genetic analysis of the Drosophila single-minded gene reveals a central nervous system influence on muscle development. Mech Dev 48:81-91
Kim, S H; Crews, S T (1993) Influence of Drosophila ventral epidermal development by the CNS midline cells and spitz class genes. Development 118:893-901
Wharton Jr, K A; Crews, S T (1993) CNS midline enhancers of the Drosophila slit and Toll genes. Mech Dev 40:141-54
Crews, S; Franks, R; Hu, S et al. (1992) Drosophila single-minded gene and the molecular genetics of CNS midline development. J Exp Zool 261:234-44

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