Abstract
The coordination of stem- and blast-cell behaviours, such as self-renewal, differentiation and quiescence, with physiological changes underlies growth, regeneration and tissue homeostasis1,2,3. Germline stem and somatic blast cells in newly hatched Caenorhabditis 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 diapause4,5,6). Although previous studies showed that the insulin/insulin-like growth factor (IGF) signalling (IIS) pathway regulates this developmental quiescence5,6,7,8, the detailed mechanism by which the IIS pathway enables these multipotent cells to respond to nutrient availability is unknown. Here we show in C. elegans that the microRNA (miRNA) miR-235, a sole orthologue of mammalian miR-92 from the oncogenic miR-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.
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Acknowledgements
We thank A. Fire, A. Frand, Y. Iino, S. Mitani, X. Wei and K. Shen for reagents and strains, and K. Iki for comments on the manuscript. Some C. elegans strains used in this study were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health National Center for Research Resources, and the MITANI Lab through the National Bio-Resource Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. This work was supported by Japan Society for the Promotion of Science KAKENHI grant numbers 23229001 (T.K.), 23370083 (K.K.), and MEXT KAKENHI grant numbers 24657081 (T.K.), 23116703 (M.F.).
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H.K., M.F. and A.K. designed and performed the experiments; all authors analysed and interpreted the data; M.F., K.K. and T.K. supervised the project; H.K. and M.F. wrote the manuscript with comments from all authors.
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Kasuga, H., Fukuyama, M., Kitazawa, A. et al. The microRNA miR-235 couples blast-cell quiescence to the nutritional state. Nature 497, 503–506 (2013). https://doi.org/10.1038/nature12117
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DOI: https://doi.org/10.1038/nature12117
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