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Epithelial differentiation and morphogenesis in Drosophila - M. Grammont

Epithelia form a vital part of all our tissues and organs. The adhesive properties of these cellular sheets and the ability of their component cells to change shape and/or to move are essential to generate a large number of tissues and organs. The general context of our research addresses the following question : what are the cellular, molecular and mechanical mechanisms that link epithelial cell differentiation to morphogenesis ?

Drosophila oogenesis provides an elegant context in which to study epithelial processes such as differentiation, change of form, displacement and migration, since they can be observed in the course of the development of a single follicle.

A follicle is composed of a growing oocyte connected to 15 nurse cells (dark and light brown, respectively), which are surrounded by a monolayer of epithelial cells, called the follicular cells. These cells undergo multiple morphogenetic processes during the growth and the maturation of the oocyte. The whole follicle contacts a basement membrane (green). Before morphogenesis, all follicular cells are cuboidal. At a particular stage of oogenesis, most of them become columnar (grey and black) and a few become squamous (pink).

The flattening occurs like a wave from anterior to posterior. The number of squamous cells (green) depends on their ability to flatten (Stereotyped adherens junction remodelling, in red), on the germline growth and on interactions with the basement membrane. We seek to identify the genes involved in stretched cell differentiation and in cell shape changes in order to understand the chronological and stereotype progression of cell flattening. In parallel, we determine the mechanical properties of the germline cells, the follicular cells and the basement membrane. Indeed, our aim is to measure comprehensively the physical properties of cells and tissues, and to unravel the molecular mechanisms allowing shape changes in response to extrinsic physical forces. To do so, we combine molecular tools, morphometry, and physical measurements, and we integrate these data in computational models, which we will test using mutants, pharmacology and physical manipulations of cells, so as to obtain an integrated view of morphogenesis.