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• Function of nuage
• Maintenance and establishment of germline stem cells and the niche in fly ovary
• Germline stem cells in vertebrates

Research Projects

Drosophila melanogaster have germline stem cells (GSCs) in their ovaries. GSCs provide all the germline cells for egg production, so that fly females keep laying eggs throughout their entire life cycle (Fig 1). It has been shown that these germline stem cells reside in a specific micro-environment, a niche, and remain undifferentiated. Somatic cells called cap cells (CpC) are the main of the niche: they are tightly associated with GSCs, and providing fly BMP2/4 homolog, Decapentaplegic (Dpp). Dpp represses the expression of Bam (Bag-of-Marble) which triggers differentiation. Germline stem cell divides asymmetrically, one remains in a niche as a stem cell, and the other one, cystoblast, leaves a niche and starts differentiation into cyst by the release of Bam expression (Fig 2). Cystoblast undergoes 4 synchronous mitotic divisions with incomplete cytokinesis, and becomes 16-cell cyst in which each cells are interconnected via ring canals. During this cyst formation, a unique organelle called fusome grows asymmetrically and spans through ring canals. Eventually one of those cells with four ring canals will differentiate into oocyte, and others will be nurse cells. Using this system as a model, we are studying the nature of GSC, the role of the niche, and the molecular mechanism of earlier differentiation into cysts after their departure of the niche.

Figure 1 fly germarium

Figure 2: cyst formation

1) We identified novel fly genes, Kumo and Krimp, expressed very strongly in early stages of germline cells including stem cells. Interestingly, these protein turned out to be components of nuage (Fig 3). Nuage is a well-known perinuclear electron-dense granule, a hallmark of germline cells across the animal kingdom. Despite of its evolutionary conservation, the role of nuage in germline cells remains unclear.  The study of Kumo and Krimp will lead us to better understanding of the role of nuage in the early germline cells. 

2) Maintenance and establishment of germline stem cells and the niche in fly ovary
From the gene profile of purified GSC (Kai et al, 2005), we have found a large number of candidate genes which may be involved in establishment and maintenance of GSC. We will perform the screening of those genes to identify ‘stemness’ genes. Also we will perform the profiling of the niche cells (cap cells) for GSC to find out any key genes for the niche activity.

3) Germline stem cells in vertebrates
Although the presence of germline stem cells in mouse ovary has been shown, so many questions remain to be addressed: Does the niche for stem cells exist? What kind of structure keeps stem cells undifferentiated? How they are differentiating? Our preliminary data from Xenopus ovary and other mouse study suggest that vertebrate female germline stem cells seem to reside in a specific region (a niche) and differentiate into cysts as Drosophila. We will address those questions by using zebrafish as a vertebrate model system.