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Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis

During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able t...

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Autores principales: Carucci, Nicoletta, Cacci, Emanuele, Nisi, Paola S., Licursi, Valerio, Paul, Yu-Lee, Biagioni, Stefano, Negri, Rodolfo, Rugg-Gunn, Peter J., Lupo, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society Publishing 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414248/
https://www.ncbi.nlm.nih.gov/pubmed/28484611
http://dx.doi.org/10.1098/rsos.160913
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author Carucci, Nicoletta
Cacci, Emanuele
Nisi, Paola S.
Licursi, Valerio
Paul, Yu-Lee
Biagioni, Stefano
Negri, Rodolfo
Rugg-Gunn, Peter J.
Lupo, Giuseppe
author_facet Carucci, Nicoletta
Cacci, Emanuele
Nisi, Paola S.
Licursi, Valerio
Paul, Yu-Lee
Biagioni, Stefano
Negri, Rodolfo
Rugg-Gunn, Peter J.
Lupo, Giuseppe
author_sort Carucci, Nicoletta
collection PubMed
description During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.
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spelling pubmed-54142482017-05-08 Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis Carucci, Nicoletta Cacci, Emanuele Nisi, Paola S. Licursi, Valerio Paul, Yu-Lee Biagioni, Stefano Negri, Rodolfo Rugg-Gunn, Peter J. Lupo, Giuseppe R Soc Open Sci Cellular and Molecular Biology During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals. The Royal Society Publishing 2017-04-05 /pmc/articles/PMC5414248/ /pubmed/28484611 http://dx.doi.org/10.1098/rsos.160913 Text en © 2017 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Cellular and Molecular Biology
Carucci, Nicoletta
Cacci, Emanuele
Nisi, Paola S.
Licursi, Valerio
Paul, Yu-Lee
Biagioni, Stefano
Negri, Rodolfo
Rugg-Gunn, Peter J.
Lupo, Giuseppe
Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis
title Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis
title_full Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis
title_fullStr Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis
title_full_unstemmed Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis
title_short Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis
title_sort transcriptional response of hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis
topic Cellular and Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414248/
https://www.ncbi.nlm.nih.gov/pubmed/28484611
http://dx.doi.org/10.1098/rsos.160913
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