The application entails studies of the transcriptional regulation and function of neuropeptide transmitters in the Drosophila nervous system. During the previous funding period it was found that in a subset of dFMRFergic neurons, this peptide is upregulated after a 5h delay by the LIM domain gene apterous. Genetic screens are proposed to isolate factors downstream of apterous. A yeast two-hybrid screen is proposed to identify homeodomain transcription factors that regulate dFMRFa in another neuronal type, OL2.
In aim 2, the expression patterns of two enzymes involved in neuropeptide amidation, dPHM and dPAL, will be analyzed.
Aim 3 focuses on the regulation of these amidation enzymes. Promoter constructs will be made to identify the minimal sequences driving lacZ in the normal pattern. Promoter constructs will be used in the background of apterous mutations to investigate whether this gene also drives the amidation enzymes in the same sets of neurons that express dFMRFa. Another gene identified in the previous granting period, dimmed, will be characterized genetically and molecularly in aim 4. In dimmed mutant embryos, the dFMRFa expression is globally decreased without concomitant morphological abnormalities.
Aim 5 is a collaborative effort between the investigator and Drs. Hall and Meinertzhagen to investigate the function of dFMRFa in the OL2 neurons that have been implicated in circadian rhythmicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021749-17
Application #
6393365
Study Section
Special Emphasis Panel (ZRG1-MDCN-6 (01))
Program Officer
Leblanc, Gabrielle G
Project Start
1985-07-01
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
17
Fiscal Year
2001
Total Cost
$303,150
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Diao, Feici; Mena, Wilson; Shi, Jonathan et al. (2016) The Splice Isoforms of the Drosophila Ecdysis Triggering Hormone Receptor Have Developmentally Distinct Roles. Genetics 202:175-89
Beebe, Katherine; Park, Dongkook; Taghert, Paul H et al. (2015) The Drosophila Prosecretory Transcription Factor dimmed Is Dynamically Regulated in Adult Enteroendocrine Cells and Protects Against Gram-Negative Infection. G3 (Bethesda) 5:1517-24
Hadži?, Tarik; Park, Dongkook; Abruzzi, Katharine C et al. (2015) Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED. Nucleic Acids Res 43:2199-215
Park, Dongkook; Li, Peiyao; Dani, Adish et al. (2014) Peptidergic cell-specific synaptotagmins in Drosophila: localization to dense-core granules and regulation by the bHLH protein DIMMED. J Neurosci 34:13195-207
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Park, Dongkook; Hou, Xiaowen; Sweedler, Jonathan V et al. (2012) Therapeutic peptide production in Drosophila. Peptides 36:251-6
Mills, Jason C; Taghert, Paul H (2012) Scaling factors: transcription factors regulating subcellular domains. Bioessays 34:10-6
Park, Dongkook; Hadži?, Tarik; Yin, Ping et al. (2011) Molecular organization of Drosophila neuroendocrine cells by Dimmed. Curr Biol 21:1515-24
Hamanaka, Yoshitaka; Park, Dongkook; Yin, Ping et al. (2010) Transcriptional orchestration of the regulated secretory pathway in neurons by the bHLH protein DIMM. Curr Biol 20:9-18
Park, Dongkook; Taghert, Paul H (2009) Peptidergic neurosecretory cells in insects: organization and control by the bHLH protein DIMMED. Gen Comp Endocrinol 162:2-7

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