Notch signaling promotes continued mitotic divisions in the C. elegans germ line, a control that maintains stem cells responsible for self-renewal and continued production of gametes. By contrast, Ras/Mitogen-activated protein kinase (MAPK), called MPK-1 in nematodes, promotes progression from pachytene to diplotene and entry into meiosis I in the proximal germline. To explore a potential regulatory link between Notch signaling and regulation of MPK-1 in the germ line, we focused on
lip-1, a key regulator of MAP kinase activity and probable Notch target (1). LIP-1 is a dual specificity phosphatase of a conserved class that inhibits MAPK activity (1). During vulval development, Notch signaling activates
lip-1 and thereby inactivates MPK-1 to induce secondary vulva fates in the ventral hypodermis (1). To investigate whether
lip-1 is activated by Notch signaling in the distal germ line, we carried out Chromatin Immunoprecipitation (ChIP) experiments using affinity purified LAG-3 antibodies. We IPd LAG-3 from wild-type animals or from
glp-1 mutants that have no germ line, and then performed PCR to assay specific regions of
lip-1 in the precipitate. We found that the
lip-1 promoter coimmunoprecipitated with LAG-3 antibodies from wild-type adults, but not from
glp-1 mutant adults; furthermore, the
lip-1 coding region did not IP. We suggest that
lip-1 may be a direct target of the GLP-1/Notch signaling in the adult C. elegans germ line. We are currently asking whether
lip-1 affects germline proliferation. Progress will be reported at the meeting. Reference 1. Berset et al. (2001) Notch inhibition of RAS signaling through MAP kinase phosphatase LIP-1 during C. elegans vulval development. Science 291, 1055-1058.