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Development ePress online publication date 11 Jan 2006
doi: 10.1242/dev.02232
Research article
Inhibition of germline proliferation during C. elegans dauer development requires PTEN, LKB1 and AMPK signalling
Patrick Narbonne
and
Richard Roy*
* Author for correspondence (e-mail: richard.roy{at}mcgill.ca)
In C. elegans, reduced insulin-like signalling induces developmental quiescence, reproductive delay and lifespan extension. We show here that the C. elegans orthologues of LKB1 and AMPK cooperate during conditions of reduced insulin-like signalling to establish cell cycle quiescence in the germline stem cell population, in addition to prolonging lifespan. The inactivation of either protein causes aberrant germline proliferation during diapause-like 'dauer' development, whereas the loss of AMPK uncouples developmental arrest from lifespan extension. Reduced TGF-
activity also triggers developmental quiescence independent of the insulin-like pathway. Our data suggest that these two signalling pathways converge on the C. elegans PTEN orthologue to coordinate germline proliferation with somatic development during dauer formation, via the regulation of AMPK and its upstream activator LKB1, rather than through the canonical insulin-like signalling cascade. In humans, germline mutations in TGF- family members, PTEN or LKB1 result in related tumour-predisposing syndromes. Our findings establish a developmental relationship that may underscore their shared, characteristic aetiology.
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