Pickering, J., Chinnaiya, K. and Towers, M. (2019) An autoregulatory cell cycle timer integrates growth and specification in chick wing digit development. eLife, 8. 47625.
Abstract
A fundamental question is how proliferation and growth 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 are widely applicable to many tissues.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
Keywords: | Shh; chicken; developmental biology; digits; growth; limb; patterning; timing |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 202756/Z/16/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Oct 2019 12:28 |
Last Modified: | 30 Oct 2019 12:28 |
Status: | Published |
Publisher: | eLife Sciences Publications, Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/elife.47625 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:152718 |