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Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification
During neural development, spatially regulated expression of specific transcription factors is crucial for central nervous system (CNS) regionalization, generation of neural precursors (NPs) and subsequent differentiation of specific cell types within defined regions. A critical role in dopaminergic...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519900/ https://www.ncbi.nlm.nih.gov/pubmed/23240065 http://dx.doi.org/10.1371/journal.pone.0051798 |
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author | Soldati, Chiara Cacci, Emanuele Biagioni, Stefano Carucci, Nicoletta Lupo, Giuseppe Perrone-Capano, Carla Saggio, Isabella Augusti-Tocco, Gabriella |
author_facet | Soldati, Chiara Cacci, Emanuele Biagioni, Stefano Carucci, Nicoletta Lupo, Giuseppe Perrone-Capano, Carla Saggio, Isabella Augusti-Tocco, Gabriella |
author_sort | Soldati, Chiara |
collection | PubMed |
description | During neural development, spatially regulated expression of specific transcription factors is crucial for central nervous system (CNS) regionalization, generation of neural precursors (NPs) and subsequent differentiation of specific cell types within defined regions. A critical role in dopaminergic differentiation in the midbrain (MB) has been assigned to the transcription factor Nurr1. Nurr1 controls the expression of key genes involved in dopamine (DA) neurotransmission, e.g. tyrosine hydroxylase (TH) and the DA transporter (DAT), and promotes the dopaminergic phenotype in embryonic stem cells. We investigated whether cells derived from different areas of the mouse CNS could be directed to differentiate into dopaminergic neurons in vitro by forced expression of the transcription factor Nurr1. We show that Nurr1 overexpression can promote dopaminergic cell fate specification only in NPs obtained from E13.5 ganglionic eminence (GE) and MB, but not in NPs isolated from E13.5 cortex (CTX) and spinal cord (SC) or from the adult subventricular zone (SVZ). Confirming previous studies, we also show that Nurr1 overexpression can increase the generation of TH-positive neurons in mouse embryonic stem cells. These data show that Nurr1 ability to induce a dopaminergic phenotype becomes restricted during CNS development and is critically dependent on the region of NPs derivation. Our results suggest that the plasticity of NPs and their ability to activate a dopaminergic differentiation program in response to Nurr1 is regulated during early stages of neurogenesis, possibly through mechanisms controlling CNS regionalization. |
format | Online Article Text |
id | pubmed-3519900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35199002012-12-13 Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification Soldati, Chiara Cacci, Emanuele Biagioni, Stefano Carucci, Nicoletta Lupo, Giuseppe Perrone-Capano, Carla Saggio, Isabella Augusti-Tocco, Gabriella PLoS One Research Article During neural development, spatially regulated expression of specific transcription factors is crucial for central nervous system (CNS) regionalization, generation of neural precursors (NPs) and subsequent differentiation of specific cell types within defined regions. A critical role in dopaminergic differentiation in the midbrain (MB) has been assigned to the transcription factor Nurr1. Nurr1 controls the expression of key genes involved in dopamine (DA) neurotransmission, e.g. tyrosine hydroxylase (TH) and the DA transporter (DAT), and promotes the dopaminergic phenotype in embryonic stem cells. We investigated whether cells derived from different areas of the mouse CNS could be directed to differentiate into dopaminergic neurons in vitro by forced expression of the transcription factor Nurr1. We show that Nurr1 overexpression can promote dopaminergic cell fate specification only in NPs obtained from E13.5 ganglionic eminence (GE) and MB, but not in NPs isolated from E13.5 cortex (CTX) and spinal cord (SC) or from the adult subventricular zone (SVZ). Confirming previous studies, we also show that Nurr1 overexpression can increase the generation of TH-positive neurons in mouse embryonic stem cells. These data show that Nurr1 ability to induce a dopaminergic phenotype becomes restricted during CNS development and is critically dependent on the region of NPs derivation. Our results suggest that the plasticity of NPs and their ability to activate a dopaminergic differentiation program in response to Nurr1 is regulated during early stages of neurogenesis, possibly through mechanisms controlling CNS regionalization. Public Library of Science 2012-12-11 /pmc/articles/PMC3519900/ /pubmed/23240065 http://dx.doi.org/10.1371/journal.pone.0051798 Text en © 2012 Soldati et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Soldati, Chiara Cacci, Emanuele Biagioni, Stefano Carucci, Nicoletta Lupo, Giuseppe Perrone-Capano, Carla Saggio, Isabella Augusti-Tocco, Gabriella Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification |
title | Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification |
title_full | Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification |
title_fullStr | Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification |
title_full_unstemmed | Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification |
title_short | Restriction of Neural Precursor Ability to Respond to Nurr1 by Early Regional Specification |
title_sort | restriction of neural precursor ability to respond to nurr1 by early regional specification |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519900/ https://www.ncbi.nlm.nih.gov/pubmed/23240065 http://dx.doi.org/10.1371/journal.pone.0051798 |
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