Chordin-induced Lineage Plasticity of Adult SVZ Neuroblasts After Demyelination

Nat Neurosci. 2010 May;13(5):541-550. doi: 10.1038/nn.2536. Epub 2010 Apr 25.

Abstract

The mechanisms that regulate the developmental potential of adult neural progenitor populations under physiological and pathological conditions remain poorly defined. Glutamic acid decarboxylase 65 (GAD65)- and Doublecortin (Dcx)-expressing cells constitute major progenitor populations in the adult mouse subventricular zone (SVZ). Under normal physiological conditions, SVZ-derived GAD65-positive and Dcx-positive cells expressed the transcription factor Pax6 and migrated along the rostral migratory stream to the olfactory bulb to generate interneurons. After lysolecithin-induced demyelination of corpus callosum, however, these cells altered their molecular and cellular properties and migratory path. Demyelination upregulated chordin in the SVZ, which redirected GAD65-positive and Dcx-positive progenitors from neuronal to glial fates, generating new oligodendrocytes in the corpus callosum. Our findings suggest that the lineage plasticity of SVZ progenitor cells could be a potential therapeutic strategy for diseased or injured brain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / drug effects*
  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Cell Lineage / drug effects*
  • Cell Lineage / genetics
  • Cell Movement / drug effects
  • Cerebral Ventricles / pathology*
  • Corpus Callosum / cytology
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / pathology*
  • Gene Expression Regulation / drug effects
  • Glutamate Decarboxylase / genetics
  • Glycoproteins / pharmacology*
  • Green Fluorescent Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / pharmacology*
  • Lysophosphatidylcholines
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / genetics
  • Myelin Basic Protein / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurogenesis / drug effects
  • Neurogenesis / genetics
  • Neuronal Plasticity / drug effects
  • Neurons / drug effects*
  • Neurons / physiology
  • Neuropeptides / genetics
  • Oligodendroglia / drug effects
  • Oligodendroglia / physiology

Substances

  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Lysophosphatidylcholines
  • Microtubule-Associated Proteins
  • Myelin Basic Protein
  • Nerve Tissue Proteins
  • Neuropeptides
  • doublecortin protein
  • Green Fluorescent Proteins
  • chordin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2
  • Bromodeoxyuridine

Associated data

  • GEO/GSE21310