Ascl1/Mash1 is required for the development of central serotonergic neurons

Nat Neurosci. 2004 Jun;7(6):589-95. doi: 10.1038/nn1247. Epub 2004 May 9.

Abstract

The transcriptional control of the differentiation of central serotonergic (5-HT) neurons in vertebrates has recently come under scrutiny and has been shown to involve the homeobox genes Nkx2-2 and Lmx1b, the Ets-domain gene Pet1 (also known as Fev) and the zinc-finger gene Gata3. The basic helix-loop-helix (bHLH) gene Ascl1 (also known as Mash1) is coexpressed with Nkx2-2 in the neuroepithelial domain of the hindbrain, which gives rise to 5-HT neurons. Here we show in the mouse that Ascl1 is essential for the birth of 5-HT neurons, both as a proneural gene for the production of postmitotic neuronal precursors and as a determinant of the serotonergic phenotype for the parallel activation of Gata3, Lmx1b and Pet1. Thus Ascl1, which is essential for noradrenergic differentiation, is also a determinant of the serotonergic phenotype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • Neurons / metabolism*
  • Rhombencephalon / embryology*
  • Rhombencephalon / metabolism*
  • Serotonin / biosynthesis*
  • Serotonin / genetics
  • Transcription Factors / biosynthesis*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Transcription Factors
  • Serotonin