Lin28 and let-7 regulate the timing of cessation of murine nephrogenesis
Authors: Melissa H Little
Helen Montie
Melissa A Kinney
Sean B Wilson
Alexander N Combes
Daisy A Robinton
Alena V Yermalovich
Jihan K Osborne
Areum Han
Dan S Pearson
Michael J Chen
George Q Daley
Patricia Sousa
Journal: Nature Communications (2019)
Discipline: Multidisciplinary
Keywords: nephron formation; developmental timing; Lin28b; let-7; kidney development
Affiliations: Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Boston, MA, 02115, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA., Harvard Stem Cell Institute, Boston, MA, 02115, USA., Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville, Melbourne, 3052, Australia., Department of Anatomy and Neuroscience, Faculty of Science, Building 181, Corner of Grattan Street and Royal Parade, University of Melbourne, Parkville, 3010, Australia., Murdoch Childrens Research Institute, Royal Children's Hospital, 50 Flemington Rd, Parkville, Melbourne, 3052, Australia. ., Department of Pediatrics, The University of Melbourne, Level 2 West, The Royal Children's Hospital, 50 Flemington Road, Parkville, 3010, Australia. ., Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Boston, MA, 02115, USA. ., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA. ., Harvard Stem Cell Institute, Boston, MA, 02115, USA. .

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. 

Retracted: No

PubPeer comments:
 Image duplication. ![file] , 
 Unexpected uniformity in Serum creatinine level in fig. 3g. The data points are shown as in lattice points. The data points came from 14 independent animals, not mere technical replicates. I initially thought it would represent the feature of this assay. But the other data points of serum creatinine level at fig. 5k did not follow the the same rule... ![file] , 
 https: www.nature.com articles s41467-020-14944-3 Correction to: Nature Communications https: doi.org 10.1038 s41467-018-08127-4, published online 11 January 2019. The original version of this Article contained an error in Fig. 2b, in which the P21 LIN28B Wt1 panel was inadvertently duplicated and the same panel used for the P14 image in error. Author notes These authors contributed equally: Alena V. Yermalovich, Jihan K. Osborne. ![file] ,