1. Developmental Biology
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Branching morphogenesis in the developing kidney is not impacted by nephron formation or integration

  1. Kieran M Short
  2. Alexander Combes
  3. Valerie Lisnyak
  4. James Lefevre
  5. Lynelle Jones
  6. Melissa H Little
  7. Nicholas Hamilton
  8. Ian Macleod Smyth  Is a corresponding author
  1. Monash University, Australia
  2. Murdoch Childrens Research Institute, Australia
  3. University of Queensland, Australia
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Cite this article as: eLife 2018;7:e38992 doi: 10.7554/eLife.38992

Abstract

Branching morphogenesis of the ureteric bud is integral to kidney development; establishing the collecting ducts of the adult organ and driving organ expansion via peripheral interactions with nephron progenitor cells. A recent study suggested that termination of tip branching within the developing kidney involved stochastic exhaustion in response to nephron formation, with such a termination event representing a unifying developmental process evident in many organs. To examine this possibility we have profiled the impact of nephron formation and maturation on elaboration of the ureteric bud during mouse kidney development. We find a distinct absence of random branch termination events within the kidney or evidence that nephrogenesis impacts the branching program or cell proliferation in either tip or progenitor cell niches. Instead, organogenesis proceeds in a manner indifferent to the development of these structures. Hence stochastic cessation of branching is not a unifying developmental feature in all branching organs.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files - see appended Excel files.

Article and author information

Author details

  1. Kieran M Short

    Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    Competing interests
    No competing interests declared.
  2. Alexander Combes

    Developmental Nephrology, Murdoch Childrens Research Institute, Melbourne, Australia
    Competing interests
    No competing interests declared.
  3. Valerie Lisnyak

    Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    Competing interests
    No competing interests declared.
  4. James Lefevre

    Division of Genomics and Development of Disease, University of Queensland, Brisbane, Australia
    Competing interests
    No competing interests declared.
  5. Lynelle Jones

    Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    Competing interests
    No competing interests declared.
  6. Melissa H Little

    Kidney Development, Disease and Regeneration, Murdoch Childrens Research Institute, Melbourne, Australia
    Competing interests
    Melissa H Little, has consulted for and received research funding from Organovo Inc..
  7. Nicholas Hamilton

    Division of Genomics and Development of Disease, University of Queensland, Brisbane, Australia
    Competing interests
    No competing interests declared.
  8. Ian Macleod Smyth

    Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
    For correspondence
    ian.smyth@monash.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1727-7829

Funding

National Health and Medical Research Council (1002748)

  • Melissa H Little

Australian Research Council (DP160103100)

  • Nicholas Hamilton
  • Ian Macleod Smyth

Human Frontier Science Program (RGP0039/2011)

  • Melissa H Little
  • Ian Macleod Smyth

National Health and Medical Research Council (1063696)

  • Melissa H Little

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments in this study were assessed and approved by Monash University or the Murdoch Children's Research Institute Animal Ethics Committees (MARP/2016/144) and were conducted under applicable Australian laws governing the care and use of animals for scientific purposes.

Reviewing Editor

  1. Andrew Ewald, Johns Hopkins School of Medicine, United States

Publication history

  1. Received: June 7, 2018
  2. Accepted: July 31, 2018
  3. Accepted Manuscript published: July 31, 2018 (version 1)
  4. Version of Record published: August 29, 2018 (version 2)

Copyright

© 2018, Short et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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