A Novel Embryonic Nestin-Expressing Radial Glia-Like Progenitor Gives Rise to Zonally Restricted Olfactory and Vomeronasal Neurons

Abstract

Persistent neurogenesis is maintained throughout development and adulthood in the mouse olfactory epithelium (OE). Despite this, the identity and origin of different embryonic OE progenitors, their spatiotemporal induction and contribution to patterning during development, has yet to be delineated. Here, we show that the embryonic OE contains a novel nestin-expressing radial glia-like progenitor (RGLP) that is not found in adult OE, which is antigenically distinct from embryonic CNS radial glia. Nestin-cre-mediated lineage tracing with three different reporters reveals that only a subpopulation of nestin-expressing RGLPs activate "CNS-specific" nestin regulatory elements, and produce spatially restricted olfactory receptor neurons (ORNs) in zone 1 of the OE, and vomeronasal receptor neurons restricted to the VR1 zone. This dorsal-medial restriction of transgene-activating cells is also seen in the embryonic OE of Nestin-GFP transgenic mice, in which green fluorescent protein (GFP) is found in a subpopulation of GFP+Mash1+ neuronal progenitors, despite the fact that endogenous Nestin expression is found in RGLPs throughout the OE. Embryonic OE progenitors produce three biologically distinct colony subtypes in vitro, a subpopulation of which include nestin-expressing RGLPs during in vitro colony formation. When generated from Nestin-cre/ZEG mice, neurogenic colonies also produce GFP+Mash1+ progenitors and ORNs. We thus identify a novel neurogenic precursor, the RGLP of the OE and vomeronasal organ (VNO), and provide the first evidence for intrinsic differences in the origin and spatiotemporal potential of distinct progenitors during development of the OE and VNO.