Specification of the central noradrenergic phenotype by the homeobox gene Phox2b

Mol Cell Neurosci. 2000 Mar;15(3):235-43. doi: 10.1006/mcne.1999.0826.


The closely related homeobox genes Phox2a and Phox2b are expressed in all central and peripheral noradrenergic neurons. Our previous results have shown that Phox2a controls the differentiation of the main noradrenergic center of the brain, the locus coeruleus, but leaves unaffected the other noradrenergic centers. Here, we report that Phox2b has a wider and overlapping role, in that it is required for the differentiation of all noradrenergic centers in the brain, including the locus coeruleus. Together with the previously reported lack of dopamine-b-hydroxylase and tyrosine hydroxylase expression in the peripheral nervous system of Phox2b knock-out embryos, our present findings make Phox2b a master regulator of all central and peripheral noradrenergic differentiation. We discuss the nonredundancy of Phox2 genes and their complex partnership with the bHLH transcription factor Mash1, which is also required for the differentiation of most noradrenergic cell types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Fibers / metabolism
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Brain Stem / embryology*
  • Brain Stem / metabolism
  • Cell Differentiation
  • DNA-Binding Proteins / physiology
  • Epistasis, Genetic
  • Female
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox
  • Genes, Lethal
  • Genotype
  • Gestational Age
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Isoproterenol / pharmacology
  • Locus Coeruleus / embryology*
  • Locus Coeruleus / metabolism
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Norepinephrine / physiology*
  • Phenotype
  • Phenylephrine / pharmacology
  • Rhombencephalon / embryology
  • Rhombencephalon / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcriptional Activation


  • Adrenergic alpha-Agonists
  • Adrenergic beta-Agonists
  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • NBPhox protein
  • Nerve Tissue Proteins
  • Transcription Factors
  • Phenylephrine
  • Isoproterenol
  • Norepinephrine