The influence of tissue organization on the generation of TGF-ß signals and the function of stem cell niches in the Drosophila melanogaster germline.

• Applicant: Dr. Christian Bökel
• Subject Area: Developmental Biology
• Term: from 2008 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 94902130

The aim of the proposed study is to elucidate how tissue organization shapes stem cell niches by controlling the spreading of intercellular signals. Previous work in several systems has suggested that adhesion and signaling processes between niche and stem cells are functionally linked, and it has been proposed that the tight spatial regulation of niche signaling is achieved via a putative adhesion based “stem cell niche synapse” that however is mechanistically not well defined. We will focus on the Drosophila germ line, where signalling by the BMP type TGF-β growth factor Dpp contributes to the niche microenvironment that maintains the germline stem cell (GSC) pool. In the male the Dpp signal is tightly limited to those germline cells in direct contact with the Dpp source. Since Dpp can signal over many cell diameters in other contexts a synapse like mechanism may confine BMP spreading at the niche-GSC interface. We have recently developed GFP-based live reporters for BMP receptor activation that for the first time allow detection of the active BMP receptor population live and at subcellular resolution. As predicted by the stem cell synapse hypothesis we could show that in the fly testis signalling is confined to small patches where the GSCs contact the BMP secreting niche cells. In this project we will therefore use fly genetics and cell biological methods to perturb niche tissue organisation and functionally dissect this signalling synapse.

• DFG Programme: Research Grants