title: Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons.
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.
authors.affiliation: Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida, 33136; Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, 33136.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Goldstein
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Goss
authors.forename: Konstantinos E
authors.initials: KE
authors.lastname: Hatzistergos
authors.forename: Erika B
authors.initials: EB
authors.lastname: Rangel
authors.forename: Barbara
authors.initials: B
authors.lastname: Seidler
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Hare
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D046169:Dermoscopy; D007150:Immunohistochemistry; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009416:Nerve Regeneration / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology; D009831:Olfactory Mucosa / Q000254:growth & development / Q000293:injuries / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*
chemical_list: D019009:Proto-Oncogene Proteins c-kit
keywords: growth factor; neurogenesis; olfactory epithelium; receptor tyrosine kinase; stem cells