@article{9ca84fb904ae4ff5a6828699639ffffd,
title = "Lin28 and let-7 regulate the timing of cessation of murine nephrogenesis",
abstract = "In humans and in mice the formation of nephrons during embryonic development reaches completion near the end of gestation, after which no new nephrons are formed. The final nephron complement can vary 10-fold, with reduced nephron number predisposing individuals to hypertension, renal, and cardiovascular diseases in later life. While the heterochronic genes lin28 and let-7 are well-established regulators of developmental timing in invertebrates, their role in mammalian organogenesis is not fully understood. Here we report that the Lin28b/let-7 axis controls the duration of kidney development in mice. Suppression of let-7 miRNAs, directly or via the transient overexpression of LIN28B, can prolong nephrogenesis and enhance kidney function potentially via upregulation of the Igf2/H19 locus. In contrast, kidney-specific loss of Lin28b impairs renal development. Our study reveals mechanisms regulating persistence of nephrogenic mesenchyme and provides a rationale for therapies aimed at increasing nephron mass.",
author = "Yermalovich, {Alena V.} and Osborne, {Jihan K.} and Patricia Sousa and Areum Han and Kinney, {Melissa A.} and Chen, {Michael J.} and Robinton, {Daisy A.} and Helen Montie and Pearson, {Dan S.} and Wilson, {Sean B.} and Combes, {Alexander N.} and Little, {Melissa H.} and Daley, {George Q.}",
note = "Funding Information: We are grateful to Antony Rodriguez for the gift of the let-7 knockout animals. We thank ARCH for their assistance with maintenance of the animal colony. We would also like to thank Rod Bronson from the Rodent Histopathology core at Harvard Medical School for initial mouse tissue pathology and Tom Forbes, Royal Children{\textquoteright}s Hospital, Melbourne, and Sarah Walton, Monash University, Melbourne, for advice around pathology. A.N.C. was supported by a DECRA fellowship from the Australian Research Council and M.H.L. is a Senior Principal Research Fellow of the National Health and Medical Research Council. This project was supported by NIH F99 CA212487 predoctoral fellowship to A.V.Y., Burroughs Wellcome post-doctoral enrichment scholarship to J.K.O., NHMRC Project grant (APP1063989) to M.H.L., and NIH RO1-GM107536 and administrative supplement 03S1 to G.Q.D. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-018-08127-4",
language = "English (US)",
volume = "10",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}