Signals controlling olfactory neurogenesis

Abstract

To fulfil a chemosensory role, olfactory neurons extend dendrites externally. This makes them prone to damage; however, function is maintained thoughout life by a series of progenitors present in the olfactory epithelium. Key amongst these is the horizontal basal cell, a quiescent cell that upon stimulation proliferates slowly to give rise to transit amplifying olfactory precursors. In the embryo, the horizontal basal cell is the founding progenitor cell of the olfactory epithelium. Thus the mechanism of olfactory founder cell formation and how quiescence is regulated are not known. We identify a role for retinoic acid, a metabolite of vitamin A, in the control of olfactory neurogenesis. Normally retinoic acid is provided from the neural crest and the olfactory epithelium itself. However, excess retinoic acid promotes the formation of HBCs, and prevents progression into committed olfactory precursors. In contrast, RA depletion in chicks or mice results in dysregulation of quiescence and precocious neurogenesis. Furthermore, due to progenitor depletion over time, neurogenesis is not sustained.