1. Developmental Biology
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An autoregulatory cell cycle timer integrates growth and specification in chick wing digit development

  1. Joseph Pickering
  2. Kavitha Chinnaiya
  3. Matthew Towers  Is a corresponding author
  1. University of Sheffield, United Kingdom
Research Article
  • Cited 4
  • Views 1,093
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Cite this article as: eLife 2019;8:e47625 doi: 10.7554/eLife.47625

Abstract

A fundamental question is how growth and patterning are timed during embryogenesis. Although it has been suggested that the cell cycle could be a timer, the underlying mechanisms remain elusive. Here we describe a cell cycle timer that operates in Sonic hedgehog (Shh)-expressing polarising region cells of the chick wing bud. Our data are consistent with Shh signalling stimulating polarising region cell proliferation via Cyclin D2, and then inhibiting proliferation via a Bmp2-p27kip1 pathway. When Shh signalling is blocked, polarising region cells over-proliferate and form an additional digit, which can be prevented by applying Bmp2 or by inhibiting D cyclin activity. In addition, Bmp2 also restores posterior digit identity in the absence of Shh signalling, thus indicating that it specifies antero-posterior (thumb to little finger) positional values. Our results reveal how an autoregulatory cell cycle timer integrates growth and specification and is widely applicable to many tissues.

Data availability

Source data is provided for flow cytometry

Article and author information

Author details

  1. Joseph Pickering

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5892-5159
  2. Kavitha Chinnaiya

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3375-420X
  3. Matthew Towers

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    For correspondence
    m.towers@sheffield.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2189-4536

Funding

Wellcome (202756/Z/16/Z)

  • Joseph Pickering
  • Kavitha Chinnaiya
  • Matthew Towers

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

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: April 11, 2019
  2. Accepted: September 23, 2019
  3. Accepted Manuscript published: September 23, 2019 (version 1)
  4. Version of Record published: October 4, 2019 (version 2)

Copyright

© 2019, Pickering 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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