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Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells

BACKGROUND: The central nervous system has a complex structural organization and consists of different subdomains along the antero-posterior axis. However, questions remain about the molecular mechanisms leading to the regionalization of this organ. We used a previously developed methodology to iden...

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Autores principales: Vanbekbergen, Nele, Hendrickx, Marijke, Leyns, Luc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228095/
https://www.ncbi.nlm.nih.gov/pubmed/25352416
http://dx.doi.org/10.1186/1756-0500-7-766
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author Vanbekbergen, Nele
Hendrickx, Marijke
Leyns, Luc
author_facet Vanbekbergen, Nele
Hendrickx, Marijke
Leyns, Luc
author_sort Vanbekbergen, Nele
collection PubMed
description BACKGROUND: The central nervous system has a complex structural organization and consists of different subdomains along the antero-posterior axis. However, questions remain about the molecular mechanisms leading to the regionalization of this organ. We used a previously developed methodology to identify the novel patterning role of GDF11, a TGF-β signaling factor. FINDINGS: Using an assay based on neural differentiated mouse embryonic stem cells, GDF11 is shown to induce diencephalic (posterior forebrain), mesencephalic (midbrain) and metencephalic (anterior hindbrain) fates at the expense of telencephalic (anterior forebrain) specification. GDF11 has not previously been implicated in the early patterning of the nervous system. In addition, inhibition of the TGF-β type I receptors Alk4, Alk5 and Alk7 by the pharmacological inhibitor SB431542 caused a strong anteriorization of the cells. CONCLUSIONS: Our findings suggest that GDF11 is involved in the earliest steps of the brain patterning during neurogenesis in the vertebrate embryo and is shown to be a regionalizing factor of the regional fate in the developing brain. This regionalization is not a typical posteriorizing signal as seen with retinoic acid, FGF or BMP molecules. To our knowledge, this is the first time that GDF11 is implicated in the earliest steps of the patterning of the neural plate.
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spelling pubmed-42280952014-11-12 Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells Vanbekbergen, Nele Hendrickx, Marijke Leyns, Luc BMC Res Notes Short Report BACKGROUND: The central nervous system has a complex structural organization and consists of different subdomains along the antero-posterior axis. However, questions remain about the molecular mechanisms leading to the regionalization of this organ. We used a previously developed methodology to identify the novel patterning role of GDF11, a TGF-β signaling factor. FINDINGS: Using an assay based on neural differentiated mouse embryonic stem cells, GDF11 is shown to induce diencephalic (posterior forebrain), mesencephalic (midbrain) and metencephalic (anterior hindbrain) fates at the expense of telencephalic (anterior forebrain) specification. GDF11 has not previously been implicated in the early patterning of the nervous system. In addition, inhibition of the TGF-β type I receptors Alk4, Alk5 and Alk7 by the pharmacological inhibitor SB431542 caused a strong anteriorization of the cells. CONCLUSIONS: Our findings suggest that GDF11 is involved in the earliest steps of the brain patterning during neurogenesis in the vertebrate embryo and is shown to be a regionalizing factor of the regional fate in the developing brain. This regionalization is not a typical posteriorizing signal as seen with retinoic acid, FGF or BMP molecules. To our knowledge, this is the first time that GDF11 is implicated in the earliest steps of the patterning of the neural plate. BioMed Central 2014-10-29 /pmc/articles/PMC4228095/ /pubmed/25352416 http://dx.doi.org/10.1186/1756-0500-7-766 Text en © Vanbekbergen et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Vanbekbergen, Nele
Hendrickx, Marijke
Leyns, Luc
Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells
title Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells
title_full Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells
title_fullStr Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells
title_full_unstemmed Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells
title_short Growth differentiation Factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells
title_sort growth differentiation factor 11 is an encephalic regionalizing factor in neural differentiated mouse embryonic stem cells
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228095/
https://www.ncbi.nlm.nih.gov/pubmed/25352416
http://dx.doi.org/10.1186/1756-0500-7-766
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AT leynsluc growthdifferentiationfactor11isanencephalicregionalizingfactorinneuraldifferentiatedmouseembryonicstemcells