Les relations entre croissance et prolifération reconsidérées chez la drosophile.

Abstract

Des experiences recentes realisees sur la drosophile montrent que la stimulation des divisions cellulaires ne conduit pas a une augmentation de la masse tissulaire. L' inhibition ou l' induction de la proliferation entraine la formation de tissus de meme taille avec, respectivement, des cellules anormalement grosses ou exceptionnellement petites. Ces donnees indiquent, par ailleurs, que la croissance est dominante et limitante sur la proliferation. Cet eclairage nouveau des liens entre croissance cellulaire (augmentation de la masse) et proliferation (augmentation du nombre de cellules) conduit a reexaminer la vision de la morphogenese et de la cancerogenese en pretant davantage d' attention a la deregulation de la croissance plutot qu' a celle du cycle cellulaire.

Recent data obtained from studies on Drosophila demonstrate that cell proliferation does not equal growth. Stimulation or inhibition of the cell cycle rate leads to tissues of the same overall size as that reached in a normal situation, but these tissues are composed either of smaller cells or of larger cells respectively. These experiments have been possible thanks to the tools existing now in Drosophila such as mutations in cell cycle regulators, targeted and inducible expression of genes in transgenic animals and generation of genetic mosaics constituted of chosen mutant cells in various genetic backgrounds. These observations confirm previous findings obtained in yeast and strongly favour the idea that growth is dominant and rate limiting over proliferation. Several factors which were believed to affect proliferation by interfering directly and only with cell cycle might, in fact, primarily modify the growth rate before acting on proliferation. Similarly, it is now widely acknowledged that, in many cases, growth factors signal to the translation machinery to positively stimulate growth and this, in turn, will induce cell proliferation. These findings have important implications in our current understanding of morphogenesis. Growth and patterning of Drosophila imaginal discs appear to directly rely on a control of growth rate, in which WNT and BMP's Drosophila homologues may play a key role, rather than on a cell counting control. We also reconsider cancerogenesis in the light of these new results and of some recent functional analysis of tumor suppressor genes in Drosophila. Intriguingly, most of these genes appear to function in the control of growth and not in cell cycle regulation. Moreover, they act as positive regulators of growth rate. The challenge is now to understand why and how a cell with a disadvantage in its own growth, escapes the proliferation control and becomes tumourous.