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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...

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Autores principales: Soldati, Chiara, Cacci, Emanuele, Biagioni, Stefano, Carucci, Nicoletta, Lupo, Giuseppe, Perrone-Capano, Carla, Saggio, Isabella, Augusti-Tocco, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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