Editors' ChoiceDevelopment

Arrested Development

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Science Signaling  17 Nov 2009:
Vol. 2, Issue 97, pp. ec370
DOI: 10.1126/scisignal.297ec370

Many animals cope with unfavorable environmental or nutrient-poor conditions by entering diapause, a reversible state of metabolic dormancy and developmental arrest. The nematode Caenorhabditis elegans may enter a diapause called the dauer phase in response to starvation, high temperature, or dauer pheromone during the third larval (L3) stage. Dauer pheromone is a complex mixture of small molecules that includes glycosides called ascarosides, many of which can induce dauer formation when applied to worms in purified form. How these pheromone signals are perceived and how they are linked to the signaling pathways that drive the transition into the dauer form has been unclear. Here, Kim et al. report that two G protein–coupled receptors (GPCRs) act as pheromone receptors in the dauer pathway. SRBC-64 (serpentine receptor, class BC–64) and SRBC-66 were required specifically in a pair of chemosensory neurons for normal dauer formation in response to ascarosides. Coexpression of transgenes encoding SRBC-64 and SRBC-66 enabled a pheromone-dependent decrease in cyclic adenosine 3′,5′-monophosphate (cAMP) in human embryonic kidney (HEK) cells, indicating that these two receptors were sufficient to transduce the pheromone signal intracellularly. These two GPCRs therefore represent a route through which dauer pheromone may be sensed and linked to downstream signaling events. Whereas starvation, overcrowding, or high temperature induce dauer formation during the L3 stage, the same conditions elicit a developmentally distinct L1 diapause during the earlier L1 stage. Angelo and Van Gilst describe a third type of C. elegans diapause: an adult reproductive diapause (ARD) that is entered when animals are starved during the last larval stage, L4. In ARD, most of the germ cells undergo apoptosis, but a subset of germline stem cells are protected from degradation and can repopulate the gonad when food is restored. When released from ARD, animals become reproductively active and show a normal life span. The nuclear hormone receptor NHR-49 was required for entry into and for recovery from ARD. This is similar to the requirement for the nuclear hormone receptor Daf-12 for L3 dauer formation (see the Perspective by Ogawa and Sommer). These studies highlight the fact that not only the nature of the diapause state but also the molecular mechanisms that trigger it depend on the organism’s stage of development when diapause is initiated.

G. Angelo, M. R. Van Gilst, Starvation protects germline stem cells and extends reproductive longevity in C. elegans. Science 326, 954–958 (2009). [Abstract] [Full Text]

K. Kim, K. Sato, M. Shibuya, D. M. Zeiger, R. A. Butcher, J. R. Ragains, J. Clardy, K. Touhara, P. Sengupta, Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans. Science 326, 994–998 (2009). [Abstract] [Full Text]

A. Ogawa, R. J. Sommer, Strategies to get arrested. Science 326, 944–945 (2009). [Summary] [Full Text]

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