Comparative characterization of the human and mouse third ventricle germinal zones

J Neuropathol Exp Neurol. 2011 Jul;70(7):622-33. doi: 10.1097/NEN.0b013e31822200aa.

Abstract

Recent evidence indicates differences in neural stem cell biology in different brain regions. For example, we demonstrated that neurofibromatosis 1 (NF1) tumor suppressor gene inactivation leads to increased neural stem cell proliferation and gliogenesis in the optic chiasm and brainstem but not in the cerebral cortex. The differential effect of Nf1 inactivation in the optic nerve and brainstem (in which gliomas commonly form in children with NF1) versus the cortex (in which gliomas rarely develop) suggests the existence of distinct ventricular zones for gliomagenesis in children and in adults. Here, we characterized the third ventricle subventricular zone (tv-SVZ) in young and adult mouse and human brains. In children, but not adult humans, the tv-SVZ contains nestin-positive, glial fibrillary acidic protein-positive, brain fatty acid binding protein-positive, and sox2-positive cells with radial processes and prominent cilia. In contrast, the tv-SVZ in young mice contains sox2-positive progenitor cells and ciliated ependymal lining cells but lacks glial fibrillary acidic protein-positive, nestin-positive radial glia. As in the lateral ventricle SVZ, proliferation in the human and murine tv-SVZ decreases with age. The tv-SVZ in adult mice lacks the hypocellular subventricular zone observed in adult human specimens. Collectively, these data indicate the existence of a subventricular zone relevant to our understanding of glioma formation in children and will assist interpretation of genetically engineered mouse glioma models.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Brain / anatomy & histology*
  • Cell Proliferation
  • Child, Preschool
  • Female
  • Gene Expression Regulation, Developmental / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Infant
  • Infant, Newborn
  • Ki-67 Antigen / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission / methods
  • Middle Aged
  • Nerve Tissue Proteins / metabolism
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Sialic Acids / metabolism
  • Third Ventricle / cytology*
  • Third Ventricle / metabolism*
  • Third Ventricle / ultrastructure
  • Tubulin / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Glial Fibrillary Acidic Protein
  • Ki-67 Antigen
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecule L1
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • Sialic Acids
  • TUBB3 protein, human
  • Tubulin
  • polysialyl neural cell adhesion molecule