Postnatal Neurogenesis and Gliogenesis in the Olfactory Bulb from NG2-Expressing Progenitors of the Subventricular Zone

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⁺/β-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.