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An intrinsic cell cycle timer terminates limb bud outgrowth
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143340/ https://www.ncbi.nlm.nih.gov/pubmed/30175958 http://dx.doi.org/10.7554/eLife.37429 |
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author | Pickering, Joseph Rich, Constance A Stainton, Holly Aceituno, Cristina Chinnaiya, Kavitha Saiz-Lopez, Patricia Ros, Marian A Towers, Matthew |
author_facet | Pickering, Joseph Rich, Constance A Stainton, Holly Aceituno, Cristina Chinnaiya, Kavitha Saiz-Lopez, Patricia Ros, Marian A Towers, Matthew |
author_sort | Pickering, Joseph |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6143340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-61433402018-09-20 An intrinsic cell cycle timer terminates limb bud outgrowth Pickering, Joseph Rich, Constance A Stainton, Holly Aceituno, Cristina Chinnaiya, Kavitha Saiz-Lopez, Patricia Ros, Marian A Towers, Matthew eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2018-09-03 /pmc/articles/PMC6143340/ /pubmed/30175958 http://dx.doi.org/10.7554/eLife.37429 Text en © 2018, Pickering et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Pickering, Joseph Rich, Constance A Stainton, Holly Aceituno, Cristina Chinnaiya, Kavitha Saiz-Lopez, Patricia Ros, Marian A Towers, Matthew An intrinsic cell cycle timer terminates limb bud outgrowth |
title | An intrinsic cell cycle timer terminates limb bud outgrowth |
title_full | An intrinsic cell cycle timer terminates limb bud outgrowth |
title_fullStr | An intrinsic cell cycle timer terminates limb bud outgrowth |
title_full_unstemmed | An intrinsic cell cycle timer terminates limb bud outgrowth |
title_short | An intrinsic cell cycle timer terminates limb bud outgrowth |
title_sort | intrinsic cell cycle timer terminates limb bud outgrowth |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143340/ https://www.ncbi.nlm.nih.gov/pubmed/30175958 http://dx.doi.org/10.7554/eLife.37429 |
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