Across many species, including humans, one of the many consequences of aging is a
reduction in fertility, particularly female fertility. Intriguingly some species can preserve
fertility for longer than they otherwise would, under specific environmental conditions.
For example, various species of Drosophila enter a state called adult reproductive
diapause when they experience low temperatures and short day length. Under these
conditions they can double their lifespan while maintaining fertility. Previous work has
implicated a few genes in positive or negative regulation of adult reproductive diapause
in Drosophila. For example, the insulin pathway negatively regulates diapause,
suggesting mechanisms that are conserved with the regulation of metabolism, fertility,
and lifespan in other species including C. elegans, mice, and humans. However, our
mechanistic understanding of diapause is extremely limited, and how fertility is
preserved is unknown. We have taken advantage of powerful genetic tools in Drosophila
to carry out a genome-wide association study of diapause. This approach appears to be
highly successful, as the few known genes emerged from the analysis, such as the
insulin receptor. In addition, this screen revealed that the most highly enriched networks
of genes associated with diapause include those involved in neuronal development and
female reproduction. The neuronal development genes are striking, as they have not
previously been associated with diapause and thus offer to provide new molecular and
cellular insights. Here we propose to: 1) identify the genes controlling specific steps in
the diapause program such as entry, maintenance, exit, preservation of fecundity, and
lifespan; 2) test whether diapause genes are required during development to prepare the
animals for diapause, or function specifically in adulthood; and 3) investigate the
molecular mechanisms of germline stem cell preservation during diapause. We
anticipate that just as studies of C. elegans dauer formation illuminated general
pathways regulating metabolism, growth, reproduction and aging in animals ranging
from worms to humans, studies of Drosophila diapause offer the exciting potential to
uncover novel and general mechanisms of stem cell preservation, fertility maintenance,
and lifespan extension.