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

组织组织对果蝇种系中 TGF-α 信号生成和干细胞生态位功能的影响。

基本信息

批准号：
94902130
负责人：
Dr. Christian Bökel
金额：
--
依托单位：
Core Facility Konfokale und Multiphotonen Mikroskopie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2012-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/94902130?language=en
关键词：
influence tissue organization generation TGF

项目摘要

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.

这项研究的目的是阐明组织组织如何通过控制细胞间信号的传播来塑造干细胞龛位。先前在几个系统中的工作已经表明，小生境和干细胞之间的粘附和信号传导过程在功能上是相关的，并且已经提出小生境信号传导的紧密空间调节是通过假定的基于粘附的“干细胞小生境突触”来实现的，然而该“干细胞小生境突触”在机制上没有很好地定义。我们将重点关注果蝇生殖系，其中BMP型TGF-β生长因子Dpp的信号传导有助于维持生殖系干细胞（GSC）库的小生境微环境。在雄性中，Dpp信号严格限于与Dpp源直接接触的那些生殖系细胞。由于Dpp可以在其他情况下在许多细胞直径上发出信号，因此突触样机制可能限制BMP在利基-GSC界面处扩散。我们最近开发了基于GFP的BMP受体活化活报告基因，首次允许检测活性BMP受体群体的活细胞和亚细胞分辨率。正如干细胞突触假说所预测的那样，我们可以证明，在果蝇睾丸中，信号传导仅限于GSC接触BMP分泌小生境细胞的小块区域。因此，在这个项目中，我们将使用果蝇遗传学和细胞生物学方法来扰乱小生境组织的组织结构，并从功能上解剖这个信号突触。