Analysis of neurogenesis in a mammalian neuroepithelium: proliferation and differentiation of an olfactory neuron precursor in vitro.

Development of a culture system for mammalian olfactory epithelium has permitted the process of neurogenesis to be examined in vitro. Antibody markers allowing the unambiguous identification of putative neuroepithelial stem cells (keratin+ basal cells) and differentiated neurons (N-CAM+ olfactory receptor neurons) are described. In combination with [3H]thymidine uptake analysis, these antibodies have been used to characterize the existence, proliferation, and differentiation of the immediate neuronal precursor in this system. This cell is distinct from basal cells and rapidly sorts out from them, dividing as it migrates. Data are presented which suggest that the precursor follows a simple lineage program, dividing to give rise to two N-CAM+ daughter neurons. Although this precursor efficiently generates neurons in defined medium, neurogenesis subsequently ceases because new precursors are not produced, suggesting that epigenetic factors may regulate continual neurogenesis in this system.