1. Developmental Biology and Stem Cells
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Negative regulation of G2-M by ATR (mei-41)/Chk1(Grapes) facilitates tracheoblast growth and tracheal hypertrophy in Drosophila

  1. Amrutha Kizhedathu
  2. Archit V Bagul
  3. Arjun Guha  Is a corresponding author
  1. Institute for Stem Cell Biology and Regenerative Medicine (inStem), India
Research Article
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Cite as: eLife 2018;7:e29988 doi: 10.7554/eLife.29988

Abstract

Imaginal progenitors in Drosophila are known to arrest in G2 during larval stages and proliferate thereafter. Here we investigate the mechanism and implications of G2 arrest in progenitors of the adult thoracic tracheal epithelium (tracheoblasts). We report that tracheoblasts pause in G2 for ~48-56 h and grow in size over this period. Surprisingly, tracheoblasts arrested in G2 express drivers of G2-M like Cdc25/String (Stg). We find that mechanisms that prevent G2-M are also in place in this interval. Tracheoblasts activate Checkpoint Kinase 1/Grapes (Chk1/Grp) in an ATR/mei-41-dependent manner. Loss of ATR/Chk1 led to precocious mitotic entry ~24-32 h earlier. These divisions were apparently normal as there was no evidence of increased DNA damage or cell death. However, induction of precocious mitoses impaired growth of tracheoblasts and the tracheae they comprise. We propose that ATR/Chk1 negatively regulate G2-M in developing tracheoblasts and that G2 arrest facilitates cellular and hypertrophic organ growth.

Article and author information

Author details

  1. Amrutha Kizhedathu

    Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Archit V Bagul

    Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Arjun Guha

    Institute for Stem Cell Biology and Regenerative Medicine (inStem), Bangalore, India
    For correspondence
    arjung@instem.res.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-3753-1484

Funding

Department of Biotechnology , Ministry of Science and Technology (inStem Core Funds)

  • Amrutha Kizhedathu
  • Arjun Guha

Ramalingaswamy Fellowship, Department of Biotechnology , Ministry of Science and Technology (inStem/DBT/8241)

  • Arjun Guha

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

Reviewing Editor

  1. Bruce Edgar, Reviewing Editor, University of Utah, United States

Publication history

  1. Received: July 5, 2017
  2. Accepted: April 12, 2018
  3. Accepted Manuscript published: April 16, 2018 (version 1)

Copyright

© 2018, Kizhedathu 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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