Régulation génétique de l’adhérence intercellulaire : Ou comment les cadhérines sculptent la drosophile

Abstract

L’étonnante diversité des formes biologiques a toujours fasciné à la fois les biologist es et les physiciens. Dès les années 1970, Malcom Steinberg attribuait l’émergence spontanée de formes spécifiques à des différences d’adhérence entre cellules. Cependant, le lien entre les propriétés cellulaires des molécules d’adhérence, telles que les cadhérines, et les lois générales de la physique est resté longtemps flou. Ce n’est que très récemment que cette hypothèse a été validée à la fois par des études in vitro et, de manière spectaculaire, in vivo chez la drosophile. En effet, les outils génétiques puissants disponibles chez la drosophile ont permis de montrer que les lois de la thermodynamique et une régulation génétique simple de l’expression des cadhérines contribuaient à expliquer des processus aussi complexes que l’établissement de l’axe antéro-postérieur ou la morphogenèse de l’oeil composé.

The beauty and diversity of cell shapes have always fascinated both biologists and physicists. In the early 1950, J. Holtfreter coined the term « tissue affinities » to describe the forces behind the spontaneous shaping of groups of cells. These tissue affinites were later on related to adhesive properties of cell membranes. In the 1960, Malcom Steinberg proposed the differential adhesion hypothesis (DAH) as a physical explanation of the liquid-like behaviour oftissues and cells during morphogenesis. However, the link between the cellular properties of adhesion molecules, such as the cadherins, and the physical rules that shape the body, has remained unclear. Recent in vitro studies have now shown that surface tensions, which drive the spontaneous liquid-like behaviour of cell rearrangements, are a direct and linear function of cadherin expression levels. Tissue surface tensions thus arise from differences in intercellular adhesiveness,which validates the DAH in vitro. The DAH was also vindicated in vivoby stunning experiments in Drosophila. The powerful genetic tools available in Drosophila allow to manipulate the levels and patterns of expression of several cadherins and to create artificially differences in intercellular adhesiveness.The results showed that simple laws of thermodynamics, as well as quantitative and qualitative differences in cadherins expression were sufficient to explain processes as complex as the establishment of the anterior-posterior axis and the formation of the compound eye in Drosophila.