Partial coupling of proliferation and differentiation programs during <i>Caenorhabditis elegans</i> intestine development

Cell proliferation and differentiation are essential processes underlying multicellular organism development. Cell proliferation arrest usually precedes terminal differentiation, suggesting that these two processes may be coordinated. Here, we took advantage of the very stereotyped development of the Caenorhabditis elegans intestine to address whether the control of the proliferation and differentiation programs are systematically coupled. We show that delaying cell cycle arrest does not affect most aspects of intestinal differentiation but leads to a specific delay in the accumulation of late microvilli components. Reciprocally, we find that the differentiation factors ELT-2 and ELT-7 control cell cycle arrest specifically in posterior enterocytes. The occurrence of supernumerary divisions in the absence of ELT-2 and ELT-7 is associated with changes in the expression pattern of the cell cycle regulators cyclin B1 and CKI-1, and depends on the presence of the posterior Hox protein PHP-3. Our work thus demonstrates the existence of reciprocal interactions between cell proliferation and cell differentiation. It nevertheless also shows that these two processes are only partially coupled, suggesting the existence of additional mechanisms ensuring their temporal control.