title: Regulation of spinal interneuron differentiation by the paracrine action of glycine.
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.
authors.affiliation: Department of Pathology and Cell Biology and Groupe de recherche sur le système nerveux central, University of Montreal, Montreal, QC H3C 3J7, Canada.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Côté
authors.forename: Pierre
authors.initials: P
authors.lastname: Drapeau
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D051959:ELAV Proteins / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D007395:Interneurons / Q000502:physiology*; D018613:Microscopy, Confocal; D060172:Morpholinos / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D051762:PAX2 Transcription Factor / Q000378:metabolism; D019899:Paracrine Communication / Q000502:physiology*; D018009:Receptors, Glycine / Q000172:deficiency; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology*; D013331:Strychnine / Q000494:pharmacology; D027981:Symporters; D029867:Xenopus Proteins; D015027:Zebrafish / Q000196:embryology; D029961:Zebrafish Proteins / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051959:ELAV Proteins; D005968:Glutamate Decarboxylase; D005998:Glycine; D018684:Glycine Agents; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D060172:Morpholinos; D009419:Nerve Tissue Proteins; D051762:PAX2 Transcription Factor; D018009:Receptors, Glycine; D013331:Strychnine; D027981:Symporters; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000096922:K Cl- Cotransporters; C485184:enhanced green fluorescent protein; C425331:evx1 protein, zebrafish; C101907:neurogenin, Xenopus