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

Functionally redundant genes present a puzzle as to their evolutionary preservation, and offer an interesting opportunity for molecular specialization. In , either one of two presenilin genes ( or ) facilitate Notch activation, providing the catalytic subunit for the γ secretase proteolytic enzyme complex. For all known Notch signaling events, can mediate Notch activation, so the conservation of 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 mutants can be phenocopied by switching off /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 and 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.