Exciting News from the Adult Mouse Subventricular Zone

A commentary on Adult generation of glutamatergic olfactory bulb interneurons. In the adult mammalian brain the fore-brain subventricular zone (SVZ) is a source of olfactory bulb (OB) GABAergic neurons. It is by now well established that astrocyte-like cells via fast-amplifying progenitor cells generate neuronal precursors that mature into functional neurons (Kriegstein and Alvarez-Buylla, 2009). The potential of the adult SVZ to generate neuronal progenitors that are recruited to lesioned brain regions in various injury models, has opened up new vistas in attempting to enhance neu-rologic recovery through neuronal replacement (Lindvall and Kokaia, 2006; Zhang et al., 2008). Previous studies have established that the adult mouse SVZ contains heteroge-nous progenitor populations based on their embryonic origins and their potential to generate different subtypes of GABAergic interneurons (Merkle et al., 2007; Young et al., 2007). Brill and colleagues add a further level of complexity by demonstrating that some neural progenitors in the adult SVZ generate a subtype of glutamatergic neurons in the OB. The authors examined the transcription factors Neurogenin 2 (Neurog2), Tbr2 and Tbr1, known to be associated with acquisition of glutamatergic neuronal fate during cortical development. Using co-labeling with different transcription factors, 5-bromo-2′-deoxyuridine (BrdU) birth dating and transgenic mice with transcription factor-specifi c reporter expression, Brill et al. demonstrated line-age progression from Pax6 + /Mash1 + cells, to intermediary progenitor cells expressing Neurog2 and Tbr2 and ultimately to Tbr1 + postmitotic immature neurons. The Neurog2 + , Tbr2 + and Tbr1 + cells were only found in the dorsal region of the SVZ and proximal rostral migratory stream (RMS), as opposed to the progenitors of GABAergic interneurons, which were present over the entire SVZ. The authors next used their previously validated GLASTCre::ERT2 mice, in which the promoter of the astrocyte-specifi c glutamate transporter (GLAST) drives tamoxifen-inducible Cre recombi-nation in astroglial cells (Mori et al., 2006). Fate mapping using the GLASTCre::ERT2; R26R-CFP mice demonstrated that the Tbr2 + progenitors observed in the SVZ and RMS originated from GLAST + astro-cyte-like cells. The authors showed that proliferating cells in the adult SVZ generated a subtype of glutamatergic neuron, which based on location and morphology was categorized as a short-axon juxtaglomerular OB interneuron. Glutamatergic fate of the adult-generated neurons was confi rmed by demonstrating co-expression of vesicu-lar glutamate transporter 2 (vGluT2). Only a small fraction of adult-generated BrdU + cells in the glomerular layer of the OB were found to co-express vGluT2 (2%). …