Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain

Kazuhiro Sakurada, Mikiko Ohshima-Sakurada, Theo D. Palmer, Fred H. Gage

研究成果: Article査読

314 被引用数 (Scopus)

抄録

Adult rat-derived hippocampal progenitor cells express many of the molecules implicated in midbrain dopaminergic determination, including FGF receptors 1, 2 and 3, the sonic hedgehog receptor components Smo and Ptc, and the region-specific transcription factors Ptx3 and Nurr1. Here we use undifferentiated progenitors to probe the events leading to the dopaminergic phenotype and find that the influences of Nurr1 can be temporally and mechanistically uncoupled from the patterning influences of sonic hedgehog and FGF-8 or the more generic process of neuronal differentiation itself. In gain-of-function experiments, Nurr1 is able to activate transcription of the tyrosine hydroxylase gene by binding a response element within a region of the tyrosine hydroxylase promoter necessary for midbrain-specific expression. This activation is mediated through a retinoid X receptor independent mechanism and occurs in all precursors, regardless of differentiation status. Overexpression of Nurr1 does not affect proliferation or stimulate neuronal differentiation and has no influence on the expression of other dopaminergic markers. This uncoupling of tyrosine hydroxylase expression from other dopaminergic markers suggests that the midbrain dopaminergic identity is dictated by a combination of pan-dopaminergic (e.g., Shh/FGF-8) and region-specific (Nurr1) mechanisms.

本文言語English
ページ(範囲)4017-4026
ページ数10
ジャーナルDevelopment
126
18
出版ステータスPublished - 1999 9月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 発生生物学

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