PGC PROLIFERATION

Somatic control of primordial germ cell proliferation

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 Obiettivo del progetto (Objective)

'Control of cell proliferation is important during normal growth and, when impaired, might cause malignant transformation. While cell-autonomous control of proliferation has been studied extensively, cell proliferation in the context of a growing organ, when different populations of cells have to coordinate their growth is less well understood. We are using the ovary of the fruit fly Drosophila melanogaster as a model system for understanding how cell proliferation is controlled at the level of the developing organ. The ovary of Drosophila forms during embryogenesis. At the larval stages the somatic cells of the ovary proliferate and differentiate. The somatic niches for germ line stem cells (GSCs) form at that stage. Primordial germ cells (PGCs) also proliferate, and once the somatic niches form, a subset of PGCs become the adult GSCs. Control of PGC proliferation is therefore one of the factors that determine the number of GSCs that the organ will contain. We have performed a screen aimed at finding how PGC proliferation is controlled. Such a screen has not been attempted previously and was therefore likely to reveal novel regulators of cell proliferation. The screen uncovered both cell-autonomous and non-cell autonomous regulators of PGC proliferation. Some of the genes are known cell cycle regulators. Others are homologues of known human tumor-suppressors or oncogenes, which were never studied in the fly. Some of the genes were never shown to control cell proliferation. We propose to study the developmental role of the genes uncovered by the screen. To do so, we will first form a priority list of genes to study according to pre-determined criteria. Our highest priority genes will be those that act from somatic cells to control PGC proliferation. Our studies will provide a better appreciation of how PGC proliferation is controlled by neighboring cells, and how an organ might control the number of adult stem cells it contains.'

Introduzione (Teaser)

To study stem cell biology, European researchers used the fruit fly Drosophila melanogaster as a model organism. Project results provide novel insight into stem cell biology.

Descrizione progetto (Article)

Organ growth during development and tissue regeneration occur through a small population of cells known as stem cells. Manipulation of these cells is emerging as a powerful approach in regenerative medicine for restoring tissue from within. It is therefore essential to understand the mechanisms by which stem cells induce organ growth to perform manipulations in vivo.

In this context, scientists on the EU-funded 'Somatic control of primordial germ cell proliferation' (PGC PROLIFERATION) project used the fruit fly Drosophila melanogaster as a model organism. Germ line stem cells (GSCs) in this system exhibit similar biological principles to other stem cells in terms of maintenance and differentiation.

In female flies, the ovaries form during embryogenesis. At the larval stages, somatic niches form and maintain adult GSCs in an undifferentiated state. Upon division of GSCs, one of the daughter cells leaves the protective environment of the niche and differentiates into a cystoblast. This process is also regulated through cells called escort cells.

To unravel which somatic signalling pathways regulate GSC maintenance and differentiation, researchers performed a thorough screen. The woc gene proved to be essential for proper GSC differentiation. Flies lacking expression of this gene in their escort cells failed to maintain the GSC niche and developed ovarian tumours. Further analysis of the Woc protein, showed that it acted as a transcription factor enabling cystoblast differentiation through signal transducer and activator of transcription (Stat) signalling. This result demonstrated the so far unknown role of Stat signalling in GSC differentiation.

To explain the dual regulatory role of Stat signalling, scientists proposed a theory whereby Stat maintains the adhesion of GSC with the appropriate somatic cell type. Depending on the cell type, this contact elicits a different response within the germ cells.

Taken together, the data of the PGC PROLIFERATION study underscore the importance of adhesion between niche cells and stem cells, but also between differentiating stem cell daughters and their support cells.