Involvement of Ngn2, Tbr and NeuroD proteins during postnatal olfactory bulb neurogenesis

Abstract

Postnatal neurogenesis takes place in two brain regions, the hippocampus and the subventricular zone (SVZ). The transcriptional cascade controlling hippocampal neurogenesis has been described in detail; however, the transcriptional control of olfactory bulb neurogenesis is still not well mapped. In this study, we provide insights into the molecular events controlling postnatal olfactory bulb neurogenesis. We first show the existence of diverse neural stem cell/progenitor populations along the SVZ-rostral migratory stream (RMS) axis, focusing on those expressing the basic helix-loop-helix (bHLH) transcription factor Mash1. We provide evidence that Mash1-derived progenies generate oligodendrocytic and neuronal precursors through the transient expression of the bHLH transcription factors Olig2 and neurogenin2 (Ngn2), respectively. Furthermore, we reveal that Ngn2-positive progenies express the T-box transcription factors Tbr2 and Tbr1, which are usually present during cortical and hippocampal glutamatergic neuronal differentiation. We also highlight a cell population expressing another bHLH transcription factor, neuroD1 (ND1). The ND1-positive cells are located in the SVZ-RMS axis and also co-express Tbr2, Tbr1 and neuroD2. The observations that these cells incorporate bromodeoxyuridine and express both doublecortin and polysialylated form of neural cell adhesion molecule suggest that they are newborn neurons. Finally, using an in vitro assay, we demonstrate that Ngn2 and ND1 equally and exclusively direct differentiation of Mash1-expressing precursors into calbindin-expressing and calretinin-expressing neurons, which are both neuronal subtypes normally found in the olfactory bulb. Taken together, our data illustrate that Ngn2, neuroD and Tbr transcription factors are involved in postnatal neurogenesis in the olfactory bulb.