| 研究実績の概要 |
The purpose of this study is to clarify the function of Fibrillarin (Fbl), a RNA methyltransferase, in brain development. I have confirmed that knockout of Fbl caused microcephaly previously. In this year, to determine whether p53-dependent apoptosis is the cause of microcephaly of mutant brains, I crossed Fbl cKO mice with p53-/- and obtained Fbl flox/flox Emx1-Cre p53-/- double knockout mice (dKO). I found that brains of dKO were also smaller than control mice, indicating that microcephaly could not only explained by the apoptosis of neural stem cells (NSCs). To further examine the impact of Fbl on NSCs, I investigated cortical organization of dKO at E17. Notably, the number of neurons were significantly reduced when compared with control brains. To investigate to what extent Fbl affects temporal identity, I performed transcriptome analysis from isolated single cells with different genotypes along developmental time. Bioinformatics analysis of these data indicated that Fbl is required for temporal fate transition of NSCs. To identify the targets of Fbl, I also performed ribosome profiling using dKO mice brains and have already identified several candidates that might be controlled by Fbl.
|
| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
In this year, we analyzed Fbl mutant mice by using different approaches at both mRNA (single cell analysis) and protein levels (ribosome profiling). We proved that Fbl is an important regulator for the temporal fate transition of NSCs. Importantly, I have already identified potential targets of Fbl.
|
