Pickering, J., Rich, C.A., Stainton, H. et al. (5 more authors) (2018) An intrinsic cell cycle timer terminates limb bud outgrowth. eLife , 7. e37429. ISSN 2050-084X
Abstract
The longstanding view of how proliferative outgrowth terminates following the patterning phase of limb development involves the breakdown of reciprocal extrinsic signalling between the distal mesenchyme and the overlying epithelium (e-m signalling). However, by grafting distal mesenchyme cells from late stage chick wing buds to the epithelial environment of younger wing buds, we show that this mechanism is not required. RNA sequencing reveals that distal mesenchyme cells complete proliferative outgrowth by an intrinsic cell cycle timer in the presence of e-m signalling. In this process, e-m signalling is required permissively to allow the intrinsic cell cycle timer to run its course. We provide evidence that a temporal switch from BMP antagonism to BMP signalling controls the intrinsic cell cycle timer during limb outgrowth. Our findings have general implications for other patterning systems in which extrinsic signals and intrinsic timers are integrated.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018, Pickering et al. 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. |
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: | 05 Nov 2018 10:10 |
Last Modified: | 05 Nov 2018 10:15 |
Published Version: | https://doi.org/10.7554/eLife.37429 |
Status: | Published |
Publisher: | eLife Sciences Publications |
Refereed: | Yes |
Identification Number: | 10.7554/eLife.37429 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:137895 |
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