| Project/Area Number |
10680731
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurochemistry/Neuropharmacology
|
|---|
| Research Institution | TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH (1999)
Tokyo Metropolitan Institute for Neuroscience (1998) |
|---|
Principal Investigator |
OHSAKO Shunji TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE, STAFF SCIENTIST, 東京都神経科学総合研究所, 研究員(主任) (50152103)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAMATSU Yoshiki TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH, TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCE, STAFF SCIENTIST, 東京都神経科学総合研究所, 主事研究員 (50250204)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Neural development / Helix-Loop-Helix / Transcription / Repressor / Activator / C2HC-type Zn finger / Differentiation / Drosophila / アクティベーター / 抹消神経系 / dNZF-1 / 神経発生 / C2HC型Znフィンガー / Gal4 / UAS |
|---|
| Research Abstract |
To understand the molecular mechanisms of neural development, we are focusing on the studies of actions of basic helix-loop-helix (bHLH) activator and repressor proteins. Xenopus MyT1, whose expression is positively regulated by the bHLH protein and negatively regulated by the Notch/Delta signal transduction pathway, has recently been shown to play a critical role in neuronal differentiation. In Drosophila, the roles of the proneural genes encoding bHLH transcriptional factors and the Delta/Notch signaling pathway have been the most extensively studied. To understand the functional roles of C2HC-type zinc finger gene(s) in Drosophila neurogenesis, we cloned the cDNA of a Drosophila C2HC-type zinc finger gene (termed dNZF-1). The dNZF-1 protein is composed of 1220 amino acids and contains only two C2HC zinc fingers, whereas all vertebrate MyT/NTF proteins contain six zinc fingers. The first C2HC zinc finger of dNZF-1 shows 96.3% amino acid sequence identity with the fourth one of NZF-3, but there is little structural homology of dNZF-1 to other members outside the two zinc fingers. Gel retardation assays showed that the dNZF-1 protein is able to bind to the double copy of an AAAGTTT sequence; furthermore, it is able to activate transcription of the heat-shock 70 minimal promoter-luciferase reporter gene through this sequence in Schneider cells. Whole-mount in situ hybridization to embryos showed that dNZF-1 transcripts are expressed in neuronal subsets of the central nervous system at the late embryonic stage. Moreover, expression of a dominant negative form of dNZF-1 using the Gal4/UAS system induced embryonic lethality. Taken together, these results suggest a functional role of dNZF-1 in neuronal differentiation.
|
