Abstract
The olfactory epithelium houses chemosensory neurons, which transmit odor
information from the nose to the brain. In adult mammals, the olfactory
epithelium is a uniquely robust neuroproliferative zone, with the ability to
replenish its neuronal and non-neuronal populations due to the presence of
germinal basal cells. The stem and progenitor cells of these germinal layers,
and their regulatory mechanisms, remain incompletely defined. Here we show that
progenitor cells expressing c-Kit, a receptor tyrosine kinase marking stem cells
in a variety of embryonic tissues, are required for maintenance of the adult
neuroepithelium. Mouse genetic fate-mapping analyses show that embryonically, a
c-Kit (+) population contributes to olfactory neurogenesis. In adults
under conditions of normal turnover, there is relatively sparse c-Kit
(+) progenitor cell (ckPC) activity. However, after experimentally
induced neuroepithelial injury, ckPCs are activated such that they reconstitute
the neuronal population. There are also occasional non-neuronal cells found to
arise from ckPCs. Moreover, the selective depletion of the ckPC population,
utilizing temporally controlled targeted
diphtheria
toxin A
expression, results in failure of neurogenesis after experimental injury.
Analysis of this model indicates that most ckPCs reside among the globose basal
cell populations and act downstream of horizontal basal cells, which can serve
as stem cells. Identification of the requirement for olfactory c-Kit expressing
progenitors in olfactory maintenance provides new insight into the mechanisms
involved in adult olfactory neurogenesis. Additionally, we define an important
and previously unrecognized site of adult c-Kit activity.
