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Epigenetic cues in midbrain dopaminergic neuron development.

C Perrone-Capano1, P Da Pozzo, U di Porzio

  • 1Istituto Internazionale di Genetica e Biofisica, CNR, Naples, Italy. perrone@iigbna.iigb.na.cnr.it

Neuroscience and Biobehavioral Reviews
|February 2, 2000
PubMed
Summary

Midbrain dopaminergic neuron development relies on Sonic Hedgehog and FGF8 for initial commitment. The transcription factor Nurr1 is crucial for final determination and neurotransmission gene expression.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Midbrain dopaminergic (DA) neurons are vital for vertebrate central nervous system (CNS) functions.
  • Their development involves extracellular inducers and transcription factors for commitment and determination.

Purpose of the Study:

  • To elucidate the molecular mechanisms and developmental timeline governing midbrain DA neuron differentiation.
  • To understand the roles of extracellular signals and transcription factors in DA neuron development and function.

Main Methods:

  • Analysis of gene expression patterns during DA neuron development.
  • Investigating the roles of Sonic Hedgehog, FGF8, and Nurr1 in DA neuron differentiation.
  • Examining the influence of target tissue interactions on DA neuron function.

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Main Results:

  • Sonic Hedgehog and FGF8 induce DA neuron progenitor fate.
  • The orphan nuclear receptor Nurr1 is essential for DA neuron final determination.
  • DA neurotransmission genes are expressed sequentially, with synthesis preceding uptake.
  • Interactions with striatal target neurons modulate DA neuron function.

Conclusions:

  • Midbrain DA neuron development is a multi-step process involving specific extracellular cues and transcription factors.
  • Nurr1 plays a critical role in establishing DA neuron identity and function.
  • Developmental timing of gene expression and target tissue interactions are crucial for mature DA neuron function.