Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons

Nat Neurosci. 2006 Jun;9(6):770-8. doi: 10.1038/nn1706. Epub 2006 May 21.

Abstract

Sensory information from the periphery is integrated and transduced by excitatory and inhibitory interneurons in the dorsal spinal cord. Recent studies have identified a number of postmitotic factors that control the generation of these sensory interneurons. We show that Gsh1/2 and Ascl1 (Mash1), which are expressed in sensory interneuron progenitors, control the choice between excitatory and inhibitory cell fates in the developing mouse spinal cord. During the early phase of neurogenesis, Gsh1/2 and Ascl1 coordinately regulate the expression of Tlx3, which is a critical postmitotic determinant for dorsal glutamatergic sensory interneurons. However, at later developmental times, Ascl1 controls the expression of Ptf1a in dIL(A) progenitors to promote inhibitory neuron differentiation while at the same time upregulating Notch signaling to ensure the proper generation of dIL(B) excitatory neurons. We propose that this switch in Ascl1 function enables the cogeneration of inhibitory and excitatory sensory interneurons from a common pool of dorsal progenitors.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics*
  • Excitatory Postsynaptic Potentials / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Homeodomain Proteins / genetics*
  • Interneurons / cytology
  • Interneurons / metabolism*
  • Mice
  • Mice, Transgenic
  • Neural Inhibition / genetics
  • Neural Pathways / cytology
  • Neural Pathways / embryology
  • Neural Pathways / metabolism
  • Posterior Horn Cells / cytology
  • Posterior Horn Cells / embryology*
  • Posterior Horn Cells / metabolism
  • Receptor, Notch1 / metabolism
  • Signal Transduction / genetics
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Synaptic Transmission / genetics
  • Transcription Factors / genetics

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Gsh1 protein, mouse
  • Gsh2 protein, mouse
  • Homeodomain Proteins
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Transcription Factors
  • transcription factor PTF1