Abstract
Caenorhabditis elegans larvae can undergo developmental arrest upon entry into the dauer stage in response to suboptimal growth conditions. Dauer larvae can exit this stage in replete conditions with no reproductive consequence. During this diapause stage, the metabolic regulator AMP-activated protein kinase (AMPK) ensures that the germ line becomes quiescent to maintain germ cell integrity. Animals that lack all AMPK signalling undergo germline hyperplasia upon entering dauer, while those that recover from this stage become sterile. Neuronal AMPK expression in otherwise AMPK-deficient animals is sufficient for germline quiescence and germ cell integrity and its effects are likely mediated through an endogenous small RNA pathway. Upon impairing small RNA biosynthesis, the post-dauer fertility is restored in AMPK mutants. These data suggest that AMPK may function in neurons to relay a message through small RNAs to the germ cells to alter their quiescence in the dauer stage, thus challenging the permeability of the Weismann barrier.
Highlights
In a genetic screen conducted to identify factors that are required to maintain germline stem cell quiescence, we found that the C. elegans orthologues of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1) cooperate to maintain cell cycle quiescence in the germline stem cell population [1]
These findings suggest that AMPK impinges on the endogenous small RNA pathway to establish germline quiescence and preserve germ cell integrity, by remodelling the chromatin to adjust gene expression in the germ line both during the dauer stage and during recovery to adulthood
In the absence of this master metabolic regulator, animals exhibit germline hyperplasia during the dauer stage while mutants that recover from the diapause show a highly penetrant sterility as well as vulval defects as adults
Summary
In Caenorhabditis elegans (C. elegans), reduced insulin-like signalling induces physiological and morphological changes that can result in lifespan extension, reproductive delay, and developmental quiescence [1]. Animals will develop through the four larval stages L1 through L4, become reproductive adults, and give rise to a full brood (200–300 progeny) These divisions, and the germ line as a whole, are sensitive to environmental cues, such as energetic stressors and/or hormone signalling [7]. Mutations in somatic cells are more tolerated in C. elegans, but germ cell mutations are problematic as they can be amplified in the germ line and can be inherited throughout subsequent generations Both PAR-4 and AMPK are critical to maintain germline quiescence by halting the cell cycle in the germline stem cell population upon entering the dauer stage [2,4], and this process requires both catalytic α subunits of AMPK. One of the key effectors of the insulin signalling pathway, the phosphatase and tensin homolog (PTEN) orthologue in C. elegans (daf-18), can work with AMPK in some contexts, but in the dauer germ line, it appears to function in parallel to AMPK to suppress the germ cell divisions in the dauer stage [2,4]
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