Regulation of spinal interneuron differentiation by the paracrine action of glycine

Dev Neurobiol. 2012 Feb;72(2):208-14. doi: 10.1002/dneu.20972.

Abstract

Glycine and γ-aminobutyric acid (GABA) are depolarizing during early development but the purpose is unclear. We tested the effect of altering glycine signaling in zebrafish embryos by overexpressing the potassium-chloride co-transporter type 2 (KCC2) to reverse the chloride gradient or by blocking glycine receptors with strychnine or by selectively knocking down the embryonic glycine receptor (GlyR KD). Using a variety of markers we observed in all three cases a reduction of all types of spinal interneuron populations examined, indicating that glycine modulates their overall differentiation rather than choice of cell fate. Other cell populations (motor, sensory, and glial cells) were unaffected. As glycine appeared to act preceding neural and synaptic development, we examined the bandoneon (beo) mutant in which glycine receptors are functional but not clustered at synapses. Neural populations in beo embryos appeared normal, suggesting a paracrine action of circulating glycine in promoting interneuron differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • ELAV Proteins / metabolism
  • Glutamate Decarboxylase / metabolism
  • Glycine / metabolism*
  • Glycine Agents / pharmacology
  • Green Fluorescent Proteins
  • Homeodomain Proteins / metabolism
  • Interneurons / physiology*
  • K Cl- Cotransporters
  • Microscopy, Confocal
  • Morpholinos / pharmacology
  • Nerve Tissue Proteins
  • PAX2 Transcription Factor / metabolism
  • Paracrine Communication / physiology*
  • Receptors, Glycine / deficiency
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Spinal Cord / cytology*
  • Strychnine / pharmacology
  • Symporters
  • Xenopus Proteins
  • Zebrafish / embryology
  • Zebrafish Proteins / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • ELAV Proteins
  • Glycine Agents
  • Homeodomain Proteins
  • Morpholinos
  • Nerve Tissue Proteins
  • PAX2 Transcription Factor
  • Receptors, Glycine
  • Symporters
  • Xenopus Proteins
  • Zebrafish Proteins
  • enhanced green fluorescent protein
  • evx1 protein, zebrafish
  • neurogenin, Xenopus
  • Green Fluorescent Proteins
  • Glutamate Decarboxylase
  • Strychnine
  • Glycine