Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons

Bradley J Goldstein, Garrett M. Goss, Konstantinos E. Hatzistergos, Erika B. Rangel, Barbara Seidler, Dieter Saur, Joshua Hare

Research output: Contribution to journalArticle

29 Citations (Scopus)

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. J. Comp. Neurol. 523:15-31, 2015.

Original languageEnglish
Pages (from-to)15-31
Number of pages17
JournalJournal of Comparative Neurology
Volume523
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Regeneration
Stem Cells
Maintenance
Neurons
Neurogenesis
Olfactory Mucosa
Population
Proto-Oncogene Proteins c-kit
Diphtheria Toxin
Immunotoxins
Wounds and Injuries
Nose
Protein-Tyrosine Kinases
Mammals
Brain

Keywords

  • Growth factor
  • Neurogenesis
  • Olfactory epithelium
  • Receptor tyrosine kinase
  • Stem cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. / Goldstein, Bradley J; Goss, Garrett M.; Hatzistergos, Konstantinos E.; Rangel, Erika B.; Seidler, Barbara; Saur, Dieter; Hare, Joshua.

In: Journal of Comparative Neurology, Vol. 523, No. 1, 01.01.2015, p. 15-31.

Research output: Contribution to journalArticle

Goldstein, Bradley J ; Goss, Garrett M. ; Hatzistergos, Konstantinos E. ; Rangel, Erika B. ; Seidler, Barbara ; Saur, Dieter ; Hare, Joshua. / Adult c-Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons. In: Journal of Comparative Neurology. 2015 ; Vol. 523, No. 1. pp. 15-31.
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