The tobacco hornworm, Manduca sexta, and the fruit fly, Drosophila, are favorable experimental material in which to examine the developmental effects of hormones on the CNS. During larval life, both species show extensive neurogenesis which can be quantified by incorporation of bromodeoxyuridine into the DNA of dividing cells followed by immunocytochemistry. With this tool, the extrinsic factors regulating neurogenesis in normal larvae can be determined. Cell proliferation mutants in Drosophila will then be screened for those which interfere with various aspects of neurogenesis. Culturing of neuroblasts from mutant and wild-type animals will further clarify the role of intrinsic and extrinsic factors in regulating neurogenesis. The mechanisms by which hormones bring about the programmed death of mature neurons will be examined. Drosophila will be screened for mutants that interfere with this programmed death. Also, labeled steroids and autoradiography will be used in the moth to further define the relationship of hormone target cells to cells that die. During larval life, the insect CNS produces discrete nests of cells, each arising from a single, identifiable neuroblast. After their birth the cells arrest at a point before extensive process outgrowth and transmitter expression. Later, these cells then mature into functional neurons during metamorphosis in response to circulating ecdysteroids. A series of in vivo and in vitro experiments will examine the regulation of differentiation of these cells in response to the steroid signal. Neurons produced by specific lineages will be defined by antibodies against various transmitters. Using chemical ablation techniques, neuroblasts will be killed at various times to allow examination of the relationship of lineage size to the subsequent differentiation of its members. Specific lineage groups will be cultured and their differentiation in vitro in response to steroids will be compared to their normal fate in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS013079-18
Application #
3395096
Study Section
Neurology C Study Section (NEUC)
Project Start
1976-07-01
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
18
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Lin, Suewei; Marin, Elizabeth C; Yang, Ching-Po et al. (2013) Extremes of lineage plasticity in the Drosophila brain. Curr Biol 23:1908-13
Marin, Elizabeth C; Dry, Katie E; Alaimo, Danielle R et al. (2012) Ultrabithorax confers spatial identity in a context-specific manner in the Drosophila postembryonic ventral nervous system. Neural Dev 7:31
Scott, Janet A; Williams, Darren W; Truman, James W (2011) The BTB/POZ zinc finger protein Broad-Z3 promotes dendritic outgrowth during metamorphic remodeling of the peripheral stretch receptor dbd. Neural Dev 6:39
Truman, James W; Moats, Wanda; Altman, Janet et al. (2010) Role of Notch signaling in establishing the hemilineages of secondary neurons in Drosophila melanogaster. Development 137:53-61
Brown, Heather L D; Truman, James W (2009) Fine-tuning of secondary arbor development: the effects of the ecdysone receptor on the adult neuronal lineages of the Drosophila thoracic CNS. Development 136:3247-56
Zhou, Baohua; Williams, Darren W; Altman, Janet et al. (2009) Temporal patterns of broad isoform expression during the development of neuronal lineages in Drosophila. Neural Dev 4:39
Cornbrooks, Carson; Bland, Christin; Williams, Darren W et al. (2007) Delta expression in post-mitotic neurons identifies distinct subsets of adult-specific lineages in Drosophila. Dev Neurobiol 67:23-38
Brown, Heather L D; Cherbas, Lucy; Cherbas, Peter et al. (2006) Use of time-lapse imaging and dominant negative receptors to dissect the steroid receptor control of neuronal remodeling in Drosophila. Development 133:275-85
Williams, D W; Truman, J W (2005) Remodeling dendrites during insect metamorphosis. J Neurobiol 64:24-33
Williams, Darren W; Truman, James W (2005) Cellular mechanisms of dendrite pruning in Drosophila: insights from in vivo time-lapse of remodeling dendritic arborizing sensory neurons. Development 132:3631-42

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