Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone

J Neurosci. 2004 Nov 17;24(46):10530-41. doi: 10.1523/JNEUROSCI.3572-04.2004.

Abstract

We used a 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein (EGFP) transgenic mouse to study postnatal subventricular zone (SVZ) progenitor fate, with a focus on the olfactory bulb (OB). The postnatal OB of the CNP-EGFP mouse contained EGFP+ interneurons and oligodendrocytes. In the anterior SVZ, the majority of EGFP+ progenitors were NG2+. These NG2+/EGFP+ progenitors expressed the OB interneuron marker Er81, the neuroblast markers doublecortin (DC) and Distalless-related homeobox (DLX), or the oligodendrocyte progenitor marker Nkx2.2. In the rostral migratory stream (RMS), EGFP+ cells displayed a migrating phenotype. A fraction of these cells were either NG2-/Er81+/DC+/DLX+ or NG2+/Nkx2.2+. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) injection into the lateral ventricle (LV) of early postnatal mice demonstrated that NG2+/EGFP+ progenitors migrate from the SVZ through the RMS into the OB. Moreover, fluorescence-activated cell-sorting-purified NG2+/CNP-EGFP+ or NG2+/beta-actin-enhanced yellow fluorescent protein-positive (EYFP+) progenitors transplanted into the early postnatal LV displayed extensive rostral and caudal migration. EYFP+ or EGFP+ graft-derived cells within the RMS were DLX+/Er81+ or Nkx2.2+, migrated to the OB, and differentiated to interneurons and oligodendrocytes. In the subcortical white matter (SCWM), grafted cells differentiated to either oligodendrocytes or astrocytes. Transplantation of NG2+/EYFP+ progenitors selectively purified from the SVZ showed that these cells were migratory and generated glia and neurons in the OB, hippocampus, and striatum. In contrast, cortical, OB, or cerebellar NG2+ cells had a very limited migratory potential and gave rise to glia in the SCWM and striatum. Our findings indicate region-specific differences between NG2+ progenitor cells and show that NG2+ cells can migrate throughout the RMS and contribute to both gliogenesis and neurogenesis in the postnatal OB.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens / biosynthesis*
  • Astrocytes / cytology
  • Astrocytes / physiology
  • Brain / cytology
  • Brain / growth & development
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Cerebral Ventricles
  • Green Fluorescent Proteins / genetics
  • Homeobox Protein Nkx-2.2
  • Immunohistochemistry
  • Interneurons / cytology*
  • Interneurons / physiology
  • Mice
  • Mice, Transgenic
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism
  • Olfactory Bulb / cytology*
  • Olfactory Bulb / growth & development
  • Oligodendroglia / cytology*
  • Oligodendroglia / physiology
  • Proteoglycans / biosynthesis*
  • Stem Cell Transplantation
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • Antigens
  • Homeobox Protein Nkx-2.2
  • Nkx2-2 protein, mouse
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins