Identity, lineage and fates of a temporally distinct progenitor population in the embryonic olfactory epithelium

We defined a temporally and transcriptionally divergent precursor cohort in the medial olfactory epithelium (OE) shortly after it differentiates as a distinct tissue at mid-gestation in the mouse. This temporally distinct population of Ascl1+ cells in the dorsomedial OE is segregated from Meis1+/Pax7+ progenitors in the lateral OE, and does not appear to be generated by Pax7+ lateral OE precursors. The medial Ascl1+ precursors do not yield a substantial number of early-generated ORNs. Instead, they first generate additional proliferative precursors as well as a distinct population of frontonasal mesenchymal cells associated with the migratory mass that surrounds the nascent olfactory nerve. Parallel to these in vivo distinctions, isolated medial versus lateral OE precursors in vitro retain distinct proliferative capacities and modes of division that reflect their in vivo identities. At later fetal stages, these early dorsomedial Ascl1+ precursors cells generate spatially restricted subsets of ORNs as well as other non-neuronal cell classes. Accordingly, the initial compliment of ORNs and other OE cell types is derived from at least two distinct early precursor populations: lateral Meis1/Pax7+ precursors that generate primarily early ORNs, and a temporally, spatially, and transcriptionally distinct subset of medial Ascl1+ precursors that initially generate additional OE progenitors and apparent migratory mass cells before yielding a subset of ORNs and likely supporting cell classes.