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Lin28 and let-7 regulate the timing of cessation of murine nephrogenesis

Author

Listed:
  • Alena V. Yermalovich

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Jihan K. Osborne

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Patricia Sousa

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Areum Han

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Melissa A. Kinney

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Michael J. Chen

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Daisy A. Robinton

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Helen Montie

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Dan S. Pearson

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

  • Sean B. Wilson

    (Royal Children’s Hospital)

  • Alexander N. Combes

    (Royal Children’s Hospital
    University of Melbourne)

  • Melissa H. Little

    (Royal Children’s Hospital
    The University of Melbourne, Level 2 West, The Royal Children’s Hospital)

  • George Q. Daley

    (Children’s Hospital Boston
    Harvard Medical School
    Harvard Stem Cell Institute)

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.

Suggested Citation

  • Alena V. Yermalovich & Jihan K. Osborne & Patricia Sousa & Areum Han & Melissa A. Kinney & Michael J. Chen & Daisy A. Robinton & Helen Montie & Dan S. Pearson & Sean B. Wilson & Alexander N. Combes & , 2019. "Lin28 and let-7 regulate the timing of cessation of murine nephrogenesis," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08127-4
    DOI: 10.1038/s41467-018-08127-4
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