Patterning, Cell Specification and Feedback in the Olfactory Epithelium

Neurogenesis in the olfactory and vomeronasal epithelia proceeds through two phases: primary neurogenesis, an early morphogenetic phase in which neural stem cells and their progeny are established and expand in number; and established neurogenesis, in which cell proliferation and differentiation are balanced to maintain constant proportions of different cell populations within the olfactory epithelium (OE). Signaling molecules secreted within the epithelia and by surrounding tissues, together with stage-specific transcription factors expressed by epithelial cells, work together to direct progressive restrictions in developmental potential that occur as olfactory stem cells and committed progenitor cells produce terminally-differentiated neurons and sustentacular (supporting glial) cells. Neurogenesis and gliogenesis within the main olfactory epithelium are regulated by feedback circuits in which endogenous secreted signaling molecules regulate proliferation and fates of cells in the stem/progenitor cell pool to control neuron production. These feedback circuits are likely responsible for endowing the olfactory epithelium with its ability to respond to neuron loss by rapid and robust regeneration of its neuronal population.