English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.

Direct Regulation of Pitx3 Expression by Nurr1 in Culture and in Developing Mouse Midbrain