Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA.
Caenorhabditis elegans germline cells are maintained in an undifferentiated and mitotically dividing state by Notch signaling and the FBF (for fem-3 binding factor) RNA-binding protein. Here, we report that the LIP-1 phosphatase, a proposed homolog of mitogen-activated protein (MAP) kinase phosphatases, is required for the normal extent of germline proliferation, and that lip-1 controls germline proliferation by regulating MAP kinase activity. In wild-type germ lines, LIP-1 protein is present in the proximal third of the mitotic region, consistent with its effect on germline proliferation. We provide evidence that lip-1 expression in the germline mitotic region is controlled by a combination of GLP-1/Notch signaling and FBF repression. Unexpectedly, FBF controls the accumulation of lip-1 mRNA, and therefore is likely to control its stability or 3'-end formation. In a sensitized mutant background, LIP-1 can function as a pivotal regulator of the decision between proliferation and differentiation. The control of germline proliferation by LIP-1 has intriguing parallels with the control of stem cells and progenitor cells in vertebrates.