Program of the 2001 International Worm Meeting - Sternberg Lab ...

613
Dev. 12: 2488 (1998).
614. Identifying pathways through
which neuronal daf-2/insulin-like
signaling controls lifespan and dauer
arrest.
Catherine Wolkow, Kaveh Ashrafi,
Josie Haduong, Gary Ruvkun
Department of Molecular Biology,
Massachusetts General Hospital and Department
of Genetics, Harvard Medical School, Boston,
MA 02114
Lifespan and dauer arrest in C. elegans are
controlled by the daf-2/insulin-like signaling
pathway. In adults, mutations in daf-2, an
insulin/IGF-I receptor homolog, or age-1, a
homolog of the p110 catalytic subunit of
PI(3)K, significantly extend lifespan. In
addition, null mutations in these genes cause
constitutive arrest as dauer larvae.
614
Previously, we showed that the long lifespan of
daf-2 and age-1 mutants is rescued by restoring
daf-2 or age-1 activity to neurons. In addition,
dauer arrest in these mutants is rescued by daf-2
or age-1 expression in either neuronal or
non-neuronal cell types, although rescue from
neurons was most potent. To identify specific
neurons that control dauer arrest and lifespan,
we have expressed an age-1 cDNA from several
neuronal subtype-specific promoters in age-1
null mutants. Expressing age-1 from the
promoters for mec-7 (mechanosensory neurons),
unc-4 (motor neurons) or osm-3 (chemosensory
neurons) can rescue age-1(0) dauer arrest, but
not lifespan. This suggests that daf-2 pathway
signaling in these cell types is not sufficient for
wild-type lifespan. We are currently
investigating whether wild-type lifespan
requires age-1 activity in other neurons, or in
combinations of neurons.
The daf-2 pathway controls lifespan and dauer
arrest non-cell autonomously from neurons,
suggesting that the daf-2 pathway may regulate
downstream genes for dauer remodeling and
aging of target cells. To identify these genes, we
screened for mutations that revert the ability of
the neuronally-expressed unc-14
promoter::age-1 transgene to rescue dauer arrest
in age-1 null mutants. This screen is predicted
to identify mutations in genes that are required
for signaling from the neuronal daf-2 pathway
to the target cells that are remodeled during