Premium
Adult c‐Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons
Author(s) -
Goldstein Bradley J.,
Goss Garrett M.,
Hatzistergos Konstantinos E.,
Rangel Erika B.,
Seidler Barbara,
Saur Dieter,
Hare Joshua M.
Publication year - 2014
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23653
Subject(s) - biology , neurogenesis , olfactory epithelium , neuroepithelial cell , progenitor cell , olfactory mucosa , population , neuroscience , stem cell , olfactory ensheathing glia , microbiology and biotechnology , olfactory system , olfactory receptor , olfactory marker protein , embryonic stem cell , neural stem cell , olfactory bulb , central nervous system , genetics , gene , demography , sociology
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. J. Comp. Neurol. 523:15–31, 2015. © 2014 Wiley Periodicals, Inc.