F.GENETIC STRAINS RESEARCH CENTER
F-h. Laboratory for Frontier Research - Takako Isshiki Group

RESEARCH ACTIVITIES

(1) Analysis of temporal specification within late phases of Drosophila neuroblast lineage

Takako Isshiki and Ayumi Kusano

--During development, neural progenitors often generate diverse cell types in an invariant order, changing their property over time. Although substantial progresses have been made in understanding the molecular mechanisms of how different cell fates are generated in order, many parts of the mechanisms still remain unknown, especially in vertebrate. We utilize the Drosophila central nervous system (CNS) as an excellent model system to study temporal specification of cell fates within a lineage. We previously showed that Drosophila neuroblasts sequentially express the transcription factors Hunchback, KrU3968ppel, Pdm and Castor over time. However, most neuroblasts divide additional 10 times on average after they start expressing Castor. Thus, there must be subsequent mechanisms for temporal specification.
--To identify yet unidentified factors involved in temporal specification within neuroblast lineage, we searched a public dataset of the expression profiles of the Drosophila gene transcripts. We found several transcription factors expressed later than Castor in most neuroblasts. Next, we have investigated and elucidated the precise order of their expression. Furthermore, we start investigating how neuroblasts change their property during larval stages. Recently, it has been reported that a couple of mouse homologs of these factors are also expressed in cerebral cortex in temporally regulated manner. This fact suggests that the mechanisms we are studying might be conserved across species.

(2) Investigation of molecular functions of KrÜppel type zinc finger proteins in Development of the CNS

Ayumi Kusano

--A C. elegans heterochronic gene, lin-29, encodes a KrÜppel type zinc finger protein. Last year, we reported that Drosophila melanogaster Lin-29 is expressed transiently in neuroblast at very late stages of embryogenesis and subsequently in their late-born progeny. We have been investigating molecular functions of DmLin-29, by conducting genetic analysis. Our analysis revealed that DmLin-29 and KrÜppel have distinct functions, although they share high homology in their zinc fingers, that are thought to bind DNA directly. This fact suggests that not their zinc fingers but other parts of the proteins are mainly responsible for making the differences in their function. Aiming to elucidate the molecular mechanism that makes the differences, we have start searching proteins that can form a complex with either only one of KrÜppel or DmLin-29.

(3) In situ Detection of microRNA

Katsutomo Okamura

--Hundreds of microRNAs are found in each animal, so microRNAs are thought to have a fundamental role in regulating gene expression. Northern blot analyses of their expression strongly suggest that many microRNAs have their function in development. However, the lack of a conventional method in detecting spacio-temporal distribution of microRNA makes it very difficult to study their functions in development. Okamura has developed an efficient method for detecting mature form of microRNA in situ in Drosophila embryos. So far, he has identified a few microRNAs expressed in specific cells in the nervous system. Future analyses on neural microRNAs should provide us comprehensive understanding of gene networks that control neural cell fate specification, and may reveal novel roles for microRNAs.

PUBLICATIONS

Reviews
1. Isshiki, T. and Doe, CQ. (2004). Maintaining Youth in Drosophila Neural Progenitors. Cell Cycle. 3, 296-299.
2. 一色孝子（2004）神経幹細胞システムによる神経細胞特異化の分子機構蛋白質核酸酵素（増刊）49, 228-233.

ORAL PRESENTATIONS

草野 亜弓「ショウジョウバエ神経幹細胞系譜形成に関与する因子の探索」日本発生生物学会第37回大会、名古屋市、2004年6月