Role of the extracellular matrix during female gametogenesis in "Drosophila melanogaster"

Résumé

This work focuses on the role(s) that the extracellular matrix has during female gametogenesis in the adult Drosophila melanogaster. The extracellular matrix has an important role in a number of morphogenetic and developmentally regulated processes such as stem cell biology and the control of organ shape. The Drosophila female develops two ovaries, each composed of 16-20 egg-producing tubes called ovarioles. Eggs chambers are generated in the germarium, formed at the anterior end of each ovariole and home to two or three Germline Stem Cells (GSCs). Stem cells often reside in specialised cellular microenvironments or niches that offer stem cells structural support. In addition, signalling between support cells and stem cells is essential to regulate stem cell proliferation and to prevent their differentiation. The extracellular matrix has a fundamental role in controlling the homeostasis of stem cell niches, as it provides physical support and conveys extracellular signals. Perlecan, a heparan sulphate proteoglycan component of the extracellular matrix, has recently attracted much interest as it has been shown to act as a modulator of intercellular signals in development and morphogenesis. In this thesis we present our studies on the role of Perlecan in the maintenance of the Drosophila female germline stem cell niche and ovariole architecture. Moreover, we report the presence of different splicing isoforms of Perlecan in the basement membrane and in the interstitial matrix deposited in the GSC niche. The production of mature eggs susceptible of fertilization requires the migration of the follicular epithelium over the underlying basement membrane, a phenomenon known as egg chamber rotation. This morphogenetic event is an example of collective migration, a process in which cells maintaining stable junctions move as coordinated groups. The cooperative behaviour of migrating cells is essential and highly regulated in embryogenesis, immunity, wound healing and tumour invasion. In our work, we have quantified the levels of the only integrin functionally active during egg rotation and of one of its ligand, the extracellular component Laminin, in developing chambers. The results presented and discussed here show that Laminin amounts in the basement membrane increase with time, while integrin levels do not change significantly. We determine that the initiation and speed of egg rotation depends on the dynamic balance of integrin-Laminin amounts. Thus, the interplay of ligand-receptor levels can drive tissue migration and determine speed of migration in vivo.