Links between growth rate and proliferation revisited in Drosophila

Recent data obtained from studies on Drosophila demonstrate that cell proli feration 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 la rger cells respectively. These experiments have been possible thanks to the tools existing now in Drosophila such as mutations in cell cycle regulator s, targeted and inducible expression of genes in transgenic animals and gen eration of genetic mosaics constituted of chosen mutant cells in various ge netic backgrounds. These observations confirm previous findings obtained in yeast and strongly favour the idea that growth is dominant and rate limiti ng over proliferation. Several factors which were believed to affect prolif eration by interfering directly and only with cell cycle might, in fact, pr imarily modify the growth rate before acting on proliferation. Similarly, i t 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 Dr osophila 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. Sire 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 t o function in the control of growth and not in cell cycle regulation. Moreo ver, they act as positive regulators of growth rate. The challenge is now t o understand why and how a cell with a disadvantage in its own growth, esca pes the proliferation control and becomes tumourous.