HOP-1 Presenilin Deficiency Causes a Late-Onset Notch Signaling Phenotype That Affects Adult Germline Function in Caenorhabditis elegans.

Functionally redundant genes present a puzzle as to their evolutionary preservation, and offer an interesting opportunity for molecular specialization. In Caenorhabditis elegans, either one of two presenilin genes (sel-12 or hop-1) facilitate Notch activation, providing the catalytic subunit for the γ secretase proteolytic enzyme complex. For all known Notch signaling events, sel-12 can mediate Notch activation, so the conservation of hop-1 remains a mystery. Here, we uncover a novel "late-onset" germline Notch phenotype in which HOP-1-deficient worms fail to maintain proliferating germline stem cells during adulthood. Either SEL-12 or HOP-1 presenilin can impart sufficient Notch signaling for the establishment and expansion of the germline, but maintenance of an adult stem cell pool relies exclusively on HOP-1-mediated Notch signaling. We also show that HOP-1 is necessary for maximum fecundity and reproductive span. The low-fecundity phenotype of hop-1 mutants can be phenocopied by switching off glp-1/Notch function during the last stage of larval development. We propose that at the end of larval development, dual presenilin usage switches exclusively to HOP-1, perhaps offering opportunities for differential regulation of the germline during adulthood. Additional defects in oocyte size and production rate in hop-1 and glp-1 mutants indicate that the process of oogenesis is compromised when germline Notch signaling is switched off. We calculate that in wild-type adults, as much as 86% of cells derived from the stem cell pool function to support oogenesis. This work suggests that an important role for Notch signaling in the adult germline is to furnish a large and continuous supply of nurse cells to support the efficiency of oogenesis.