2005 Fiscal Year Final Research Report Summary
Relationships between the regulation of proliferation and development
| Project/Area Number |
13043019
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
| Allocation Type | Single-year Grants |
|---|
| Review Section |
Biological Sciences
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
NISHIDA Yasuyoshi Nagoya University, Graduate School of Science, Professor, 大学院理学研究科, 教授 (50107059)
|
|---|
| Project Period (FY) |
2001 – 2005
|
| Keywords | Drosophila / growth / cell cycle / size / mitochondria / membrane potential / BMP / Dpp |
|---|
| Research Abstract |
Each organism has specific size. The molecular mechanisms regulating the sizes of the organism and organs are largely unsolved. We have isolated a Drosophila mutant with severe growth defects. The mutant develops into small adult flies due to reduced cell size and number. Cloning of the responsive gene identified an ortholog of yeast Tim50, which locates in inner membrane of mitochondria and is involved in translocation of mitochondrial proteins while maintaining the membrane potential. Drosophila proteins also localizes in mitochondria, and we name the gene tiny tim50 (ttm50). Thus, growth in the mutant seems to be retarded due to mitochondrial dysfunction. Over-expression of ttm50 induced apoptosis, and apoptosis was completey suppressed by co-expression of baculovirus p35. In this situation, over-proliferation was induced with increased membrane potential. Thus, correlation of mitochondrial activity and proliferation was observed. To identify the singaling cascade regulating growth depending on the production of ATP in mitochondria, we have tried to screen enhancers of the ttm50 mutant. So far more than 8 loci was obtained, and we undertaking to identify the responsive genes.
There are seven genes related to ttm50 in the Drosophila genome, and they can be subgrouped into three subfamilies. We have isolated the mutants for one of the gene, Cl. The null mutant was lethal, while, in a hypomorphic mutant, both males and females were sterile. A close examination of the testis revealed an over-proliferation of spermatogonia and spermatocytes. The phenotype resembles to those observed when the Dpp, the ortholog of mammalian BMP, signals are increased So we tested the genetic interactions of Cl with the mutants in the Dpp signaling cascade, and identified Cl as a novel negative factor in the cascade. We are now trying to identify the action point of Cl in the cascade.
|
