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The coordination of stem- and blast-cell behaviours, such as selfrenewal, differentiation and quiescence, with physiological changes underlies growth, regeneration and tissue homeostasis1-3. Germline stemand somatic blast cells in newly hatchedCaenorhabditis elegans larvae can suspend postembryonic development, which consists of diverse cellular events such as migration, proliferation and differentiation, until the nutritional state becomes favourable (termed L1 diapause4-6). Although previous studies showed that the insulin/ insulin-like growth factor (IGF) signalling (IIS) pathway regulates this developmental quiescence5-8, the detailed mechanism by which the IIS pathway enables these multipotent cells to respond to nutrient availability is unknown. HereweshowinC. elegans that the microRNA (miRNA) miR-235, a sole orthologue of mammalian miR-92 from the oncogenicmiR-17-92 cluster9,10, acts in the hypodermis and glial cells to arrest postembryonic developmental events in both neuroblasts and mesoblasts. Expression of mir-235 persists during L1 diapause, and decreases upon feeding in a manner dependent on the IIS pathway. Upregulation of one of the miR-235 targets, nhr-91, which encodes an orthologue of mammalian germ cell nuclear factor, is responsible for defects caused by loss of the miRNA. Our findings establish a novel role of a miR-92 orthologue in coupling blast-cell behaviours to the nutritional state.
miRNAs are a class of small RNAs that repress expression of target messengerRNAs by base pairingwith imperfect complimentary sequences in their 39 untranslated regions (39 UTRs)11. miRNAs have been found to control various functions of stemand blast cells such as pluripotency12 and stage-specific cell fate13,14. Thus, we proposed that an miRNAhas a critical role in regulating L1 diapause. Among the stem and blast cells that initiate postembryonic development during the L1 stage, we focused on reactivation of quiescent P neuroblasts owing to ease of detection; the process first begins with migration from the ventra-lateral sides towards the ventralmidline (Fig. 1a). After screening 85 lines of miRNA mutants covering deletions of 105 individual miRNAs15, only animals carrying mir-235(n4504) showed defects in arresting migration of P neuroblasts when cultured under nutritionally poor conditions after hatch (Fig. 1b, c and Supplementary Fig. 2). n4504 deletes the entire stem-loop structure of the miR-235 miRNA, an orthologue of human miR-92 from the oncogenic miR-17-92 cluster9,10, and the putative promoter region of the adjacent protein-coding gene, T09B4.7 (Supplementary Fig. 3). In fed larval stage (L)1 larvae, migrated...