Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.

Due to their correlation with major human neurological diseases, dopaminergic neurons are some of the most studied neuronal subtypes. Mesencephalic dopaminergic (mDA) differentiation requires the activation of a cascade of transcription factors, among which play a crucial role the nuclear receptor N...

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Autores principales:	Floriana Volpicelli, Roberto De Gregorio, Salvatore Pulcrano, Carla Perrone-Capano, Umberto di Porzio, Gian Carlo Bellenchi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9402b735a5dd41ce89c6284366b6aa2e
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spelling	oai:doaj.org-article:9402b735a5dd41ce89c6284366b6aa2e2021-11-18T07:27:46ZDirect regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.1932-620310.1371/journal.pone.0030661https://doaj.org/article/9402b735a5dd41ce89c6284366b6aa2e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22363463/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Due to their correlation with major human neurological diseases, dopaminergic neurons are some of the most studied neuronal subtypes. Mesencephalic dopaminergic (mDA) differentiation requires the activation of a cascade of transcription factors, among which play a crucial role the nuclear receptor Nurr1 and the paired-like homeodomain 3, Pitx3. During development the expression of Nurr1 precedes that of Pitx3 and those of typical dopaminergic markers such as tyrosine hydroxylase (TH) and dopamine Transporter (DAT) that are directly regulated by Nurr1. Interestingly we have previously demonstrated that Nurr1 RNA silencing reduced Pitx3 transcripts, leading to the hypothesis that Nurr1 may control Pitx3 expression.Here we show that Nurr1 overexpression up-regulates that of Pitx3 in a dose-dependent manner by binding to a non-canonical NBRE consensus sequence, located at the 5' site of the gene. Interestingly, this sequence shows the same effect as the canonical one in promoting gene translation, and its deletion abolishes the ability of Nurr1 to sustain reporter gene expression. Moreover, we show that there is a direct interaction between Nurr1 and the Pitx3 gene promoter in dopaminergic cell cultures and midbrain embryonic tissue. Altogether, our results suggest that the regulation of Pitx3 by Nurr1 may be an essential event controlling the development and function of mDA neurons.Floriana VolpicelliRoberto De GregorioSalvatore PulcranoCarla Perrone-CapanoUmberto di PorzioGian Carlo BellenchiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e30661 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Floriana Volpicelli Roberto De Gregorio Salvatore Pulcrano Carla Perrone-Capano Umberto di Porzio Gian Carlo Bellenchi Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.
description	Due to their correlation with major human neurological diseases, dopaminergic neurons are some of the most studied neuronal subtypes. Mesencephalic dopaminergic (mDA) differentiation requires the activation of a cascade of transcription factors, among which play a crucial role the nuclear receptor Nurr1 and the paired-like homeodomain 3, Pitx3. During development the expression of Nurr1 precedes that of Pitx3 and those of typical dopaminergic markers such as tyrosine hydroxylase (TH) and dopamine Transporter (DAT) that are directly regulated by Nurr1. Interestingly we have previously demonstrated that Nurr1 RNA silencing reduced Pitx3 transcripts, leading to the hypothesis that Nurr1 may control Pitx3 expression.Here we show that Nurr1 overexpression up-regulates that of Pitx3 in a dose-dependent manner by binding to a non-canonical NBRE consensus sequence, located at the 5' site of the gene. Interestingly, this sequence shows the same effect as the canonical one in promoting gene translation, and its deletion abolishes the ability of Nurr1 to sustain reporter gene expression. Moreover, we show that there is a direct interaction between Nurr1 and the Pitx3 gene promoter in dopaminergic cell cultures and midbrain embryonic tissue. Altogether, our results suggest that the regulation of Pitx3 by Nurr1 may be an essential event controlling the development and function of mDA neurons.
format	article
author	Floriana Volpicelli Roberto De Gregorio Salvatore Pulcrano Carla Perrone-Capano Umberto di Porzio Gian Carlo Bellenchi
author_facet	Floriana Volpicelli Roberto De Gregorio Salvatore Pulcrano Carla Perrone-Capano Umberto di Porzio Gian Carlo Bellenchi
author_sort	Floriana Volpicelli
title	Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.
title_short	Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.
title_full	Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.
title_fullStr	Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.
title_full_unstemmed	Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.
title_sort	direct regulation of pitx3 expression by nurr1 in culture and in developing mouse midbrain.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9402b735a5dd41ce89c6284366b6aa2e
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Direct regulation of Pitx3 expression by Nurr1 in culture and in developing mouse midbrain.

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