Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pickering, Joseph, Rich, Constance A, Stainton, Holly, Aceituno, Cristina, Chinnaiya, Kavitha, Saiz-Lopez, Patricia, Ros, Marian A, Towers, Matthew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
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
_version_ 1783355960577753088
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
work_keys_str_mv AT pickeringjoseph anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT richconstancea anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT staintonholly anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT aceitunocristina anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT chinnaiyakavitha anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT saizlopezpatricia anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT rosmariana anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT towersmatthew anintrinsiccellcycletimerterminateslimbbudoutgrowth
AT pickeringjoseph intrinsiccellcycletimerterminateslimbbudoutgrowth
AT richconstancea intrinsiccellcycletimerterminateslimbbudoutgrowth
AT staintonholly intrinsiccellcycletimerterminateslimbbudoutgrowth
AT aceitunocristina intrinsiccellcycletimerterminateslimbbudoutgrowth
AT chinnaiyakavitha intrinsiccellcycletimerterminateslimbbudoutgrowth
AT saizlopezpatricia intrinsiccellcycletimerterminateslimbbudoutgrowth
AT rosmariana intrinsiccellcycletimerterminateslimbbudoutgrowth
AT towersmatthew intrinsiccellcycletimerterminateslimbbudoutgrowth