Proneural bHLH neurogenin 2 differentially regulates Nurr1-induced dopamine neuron differentiation in rat and mouse neural precursor cells in vitro

FEBS Lett. 2008 Mar 5;582(5):537-42. doi: 10.1016/j.febslet.2008.01.018. Epub 2008 Jan 31.

Abstract

Roles of Nurr1 and neurogenin 2 (Ngn2) have been shown in midbrain dopamine (DA) neuron development. We present here rat and mouse species-dependent differences of Nurr1 and Ngn2 actions in DA neuron differentiation. Nurr1 exogene expression caused an efficient generation of tyrosine hydroxylase (TH)-positive DA cells from rat neural precursor cells (NPCs). Nurr1-induced TH+ cell yields were low and highly variable depending on the origins of NPCs in mouse cultures. Coexpression of Ngn2 repressed Nurr1-induced generation of TH+ cells in rat cultures. In clear contrast, a robust enhancement in Nurr1-induced DA cell yields was observed in mouse NPCs by Ngn2. These findings imply that DA neurons may develop differently in the midbrains of these two species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Differentiation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dopamine / metabolism*
  • Gene Expression Regulation
  • Humans
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / metabolism
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Rats
  • Rats, Sprague-Dawley
  • Species Specificity
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • NEUROG2 protein, human
  • NR4A2 protein, human
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse
  • Nr4a2 protein, mouse
  • Nr4a2 protein, rat
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Transcription Factors
  • Tyrosine 3-Monooxygenase
  • Dopamine