An intrinsic cell cycle timer terminates limb bud outgrowth
- University of Sheffield, United Kingdom
- Instituto de Biomedicina y Biotecnología de Cantabria, Spain
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.
Data availability
RNA sequencing data has been deposited (https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-6437/)
Article and author information
Author details
Patricia Saiz-Lopez
Funding
Wellcome Trust (202756/Z/16/Z)
- Joseph Pickering
- Constance A Rich
- Holly Stainton
- Kavitha Chinnaiya
- Matthew Towers
Spanish Ministerio de Economia (BFU2017-88265- P)
- Cristina Aceituno
- Patricia Saiz-Lopez
- Marian A Ros
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, 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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An intrinsic cell cycle timer terminates limb bud outgrowth
eLife 7:e37429.
https://doi.org/10.7554/eLife.37429
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