Sequential generation of olfactory bulb glutamatergic neurons by Neurog2-expressing precursor cells

Abstract

BackgroundWhile the diversity and spatio-temporal origin of olfactory bulb (OB) GABAergic interneurons has been studied in detail, much less is known about the subtypes of glutamatergic OB interneurons.ResultsWe studied the temporal generation and diversity of Neurog2-positive precursor progeny using an inducible genetic fate mapping approach. We show that all subtypes of glutamatergic neurons derive from Neurog2 positive progenitors during development of the OB. Projection neurons, that is, mitral and tufted cells, are produced at early embryonic stages, while a heterogeneous population of glutamatergic juxtaglomerular neurons are generated at later embryonic as well as at perinatal stages. While most juxtaglomerular neurons express the T-Box protein Tbr2, those generated later also express Tbr1. Based on morphological features, these juxtaglomerular cells can be identified as tufted interneurons and short axon cells, respectively. Finally, targeted electroporation experiments provide evidence that while the majority of OB glutamatergic neurons are generated from intrabulbar progenitors, a small portion of them originate from extrabulbar regions at perinatal ages.ConclusionsWe provide the first comprehensive analysis of the temporal and spatial generation of OB glutamatergic neurons and identify distinct populations of juxtaglomerular interneurons that differ in their antigenic properties and time of origin.

Orchestrating transcriptional control of adult neurogenesis

“…However, Tbr2 does not appear to be required for the establishment of adult SVZ progenitors, since DCX staining in the RMS appears normal (Arnold et al 2008). Along these lines, Tbr2 expression is down-regulated as neuroblasts exit the cell cycle in the RMS, but is maintained in glutamatergic neurons in the embryo and early postnatal stages, suggesting that there may be important contextual differences between the embryo and adult environment (Winpenny et al 2011). Interestingly, Ascl1 is coexpressed with Pax6 in most type C SVZ progenitors and mediates the GABAergic phenotype, while coexpression of Ascl1 and Neurog2 is important for the glutamatergic lineage Roybon et al 2009a).…”

3-Dimensional Examination of the Adult Mouse Subventricular Zone Reveals Lineage-Specific Microdomains

“…In contrast, pallial regions contain progenitors that express Tbr2 and contribute to glutamatergic neurogenesis in the cortex [43] and olfactory bulb [44]. We next explored further this uneven distribution in the adult SVZ.…”

Adult neural stem cells: plastic or restricted neuronal fates?

“…In rodents, the two main types of glutamatergic projection neurons in the OB -mitral neurons and tufted neurons -are generated exclusively during embryonic stages (Hinds, 1968a;Hinds, 1968b;Bayer, 1983) from dorsal progenitors expressing the TFs Emx1 (Gorski et al, 2002) and Neurog2 (Winpenny et al, 2011). By sharp contrast, local circuit neurons, which are mostly GABAergic neurons that can also express dopamine (Kosaka et al, 1985;Betarbet et al, 1996;Hack et al, 2005), start to be generated embryonically by ventrolateral progenitors expressing the TF Er81 (ets variant gene 1; Etv1 -Mouse Genome Informatics) (Stenman et al, 2003), and are continuously generated throughout life by progenitors located within the whole extension of the postnatal and adult subventricular zone (SVZ) (Altman, 1969;Bayer, 1985;Luskin, 1993;BatistaBrito et al, 2008).…”