TY - JOUR
T1 - Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons
AU - Goldstein, Bradley J.
AU - Goss, Garrett M.
AU - Hatzistergos, Konstantinos E.
AU - Rangel, Erika B.
AU - Seidler, Barbara
AU - Saur, Dieter
AU - Hare, Joshua M.
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Growth factor
KW - Neurogenesis
KW - Olfactory epithelium
KW - Receptor tyrosine kinase
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=84909639109&partnerID=8YFLogxK
U2 - 10.1002/cne.23653
DO - 10.1002/cne.23653
M3 - Article
C2 - 25044230
AN - SCOPUS:84909639109
SN - 0021-9967
VL - 523
SP - 15
EP - 31
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 1
ER -