The long-term goal of this research project is to understand how regulatory genes control cell fate choice during central nervous system (CNS) development. The powerful genetics, cell biology, molecular biology, and transgenic techniques of Drosophila melanogaster will be utilized to study the development of the cells that lie along the midline of the CNS. The CNS midline cells are an experimentally simple system consisting of a small number of neurons and glia whose formation can be readily visualized and studied. Besides their roles as functional neurons and glia, they also act as a signaling center that controls axonogenesis and formation of numerous CNS and non-CNS cell types. It is proposed that the Single-minded:Tango bHLH- PAS transcription factor complex interacts combinatorially with segment polarity gene products, HMG proteins, POU homeobox proteins and other factors to specify midline neural and glial cell fates.
The aims of the project are three-fold: (1) describe how Single-minded:Tango interacts with other regulatory proteins to control midline precursor and glial cell transcription, (2) study how segment polarity gene products control the specification of midline precursor cells into midline neurons and glia, and (3) use array and enhancer trap technologies to describe global patterns of midline gene expression and how they are regulated. Together, these approaches will begin to provide a comprehensive view of the molecular control of CNS midline cell transcription and cell fate specification. Given the functional similarities in nervous system development between Drosophila and mammals, insight from this project will advance the mechanistic understanding of transcriptional control, neurogenesis, human birth defects, and obesity.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD025251-21
Application #
7448634
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Henken, Deborah B
Project Start
1993-10-01
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
21
Fiscal Year
2008
Total Cost
$308,447
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Biochemistry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Pearson, Joseph C; Crews, Stephen T (2014) Enhancer diversity and the control of a simple pattern of Drosophila CNS midline cell expression. Dev Biol 392:466-82
Manning, Laurina; Heckscher, Ellie S; Purice, Maria D et al. (2012) A resource for manipulating gene expression and analyzing cis-regulatory modules in the Drosophila CNS. Cell Rep 2:1002-13
Pearson, Joseph C; Watson, Joseph D; Crews, Stephen T (2012) Drosophila melanogaster Zelda and Single-minded collaborate to regulate an evolutionarily dynamic CNS midline cell enhancer. Dev Biol 366:420-32
Watson, Joseph D; Crews, Stephen T (2012) Formation and specification of a Drosophila dopaminergic precursor cell. Development 139:3316-25
Fontana, Joseph R; Crews, Stephen T (2012) Transcriptome analysis of Drosophila CNS midline cells reveals diverse peptidergic properties and a role for castor in neuronal differentiation. Dev Biol 372:131-42
Wheeler, Scott R; Pearson, Joseph C; Crews, Stephen T (2012) Time-lapse imaging reveals stereotypical patterns of Drosophila midline glial migration. Dev Biol 361:232-44
Freer, Stephanie M; Lau, Daniel C; Pearson, Joseph C et al. (2011) Molecular and functional analysis of Drosophila single-minded larval central brain expression. Gene Expr Patterns 11:533-46
Stagg, Stephanie B; Guardiola, Amaris R; Crews, Stephen T (2011) Dual role for Drosophila lethal of scute in CNS midline precursor formation and dopaminergic neuron and motoneuron cell fate. Development 138:2171-83
Watson, Joseph D; Wheeler, Scott R; Stagg, Stephanie B et al. (2011) Drosophila hedgehog signaling and engrailed-runt mutual repression direct midline glia to alternative ensheathing and non-ensheathing fates. Development 138:1285-95
Crews, Stephen T (2010) Axon-glial interactions at the Drosophila CNS midline. Cell Adh Migr 4:67-71

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