Neurogenesis and Regulation of Olfactory Epithelium

Ji-Sun Kim; Byung Guk Kim

doi:10.18787/jr.2019.26.1.1

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Kim and Kim: Neurogenesis and Regulation of Olfactory Epithelium

Review

Journal of Rhinology 2019; 26(1): 1-7.

Published online: 31 May 2019

DOI: https://doi.org/10.18787/jr.2019.26.1.1

Neurogenesis and Regulation of Olfactory Epithelium

Ji-Sun Kim, MD, Byung Guk Kim, MD, PhD

Department of Otorhinolaryngology-Head and Neck Surgery, Eunpyeong St. Mar's, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Corresponding author (entkbg@gmail.com)

Received 4 October 2018 Revised 3 December 2018 Accepted 26 December 2018

Journal of Rhinology

Abstract

The olfactory epithelium is capable of structural and functional recovery after injury through neurogenesis. Neurogenesis occurs via stem cells in the olfactory epithelium. Horizontal basal cells and globose basal cells in the basal layer of the epithelium have the characteristics of stem cells and progenitor cells of olfactory neurons. In order for the horizontal basal cells and globose basal cells to differentiate into olfactory neurons, distinct transcriptional factors are required at each stage. These transcription factors inhibit or synergize with each other or cells at each differentiation stage, regulating olfactory neurogenesis. Recently, the regulation of neurogenesis and development through epigenetic controls that change gene expression without changing the gene sequence have been studied. Studies of olfactory epithelium have helped to elucidate complex neurological systems including spinal cord and brain. In particular, features of neurogenesis will lead to medical advances in the treatment of central nervous diseases, which until this time have been considered impossible.

Keywords: Neurogenesis, Olfactory epithelium, Olfactory neural stem cell, Basal cell, Transcription factor

Figures and Tables

Fig. 1

Schematic illustration of the olfactory epithelium. Olfactory epithelium (OE) is a pseudostratified neuroepithelium, housing the cell bodies of mature olfactory sensory neurons (mOSN), as well as immature neurons (imOSN) produced from basal stem cells. Two populations of stem and progenitor cells, the globose basal cells (GBC) and the horizontal basal cells (HBC), support self-renewal of the OE, replacing neurons as needed. Glia-like sustentacular (Sus) and sensory microvillar (MV) cells are situated apically. Axons from OSNs exit the base of the OE and their fascicles project as the first cranial nerve (CN I) (Slightly modified from reference#1).

Fig. 2

Transcriptional regulation of cell specification in the olfactory epithelium. Progenitors including horizontal basal cells (HBCs) and globose basal cells (GBCs) require transcription factors (TFs) marked in green to be able to proliferate and survive. The neuronal lineage pathway begins with the expression of proneural TFs (such as Mash1 and Ngn1). Intermediate progenitors (IP) then differentiate under the control of differentiation TFs (such as Lhx2) to become immature olfactory sensory neuron (imOSN). imOSN subsequently undergo maturation by extension toward the apical (AL) and basal layer (BL) under the control of maturation TFs (such as OMP and O/E) to become mature sensory neurons (mOSN). Sox2/Pax6+progenitors can also choose a non-neuronal path to generate sustentacular (SUS) cells under the regulation of differentiation/maturation TFs (such as Steel and Hes1). Other non-neuronal derivatives of Sox2/Pax6+progenitors include Bowman's glands (BGs) and microvillar cells (MCs) specified by TFs marked in deep and light green respectively (Slightly modified from reference#44).

Table 1

Studies of epigenetic factors in olfactory epithelium development

cKO: conditional knock-out, dKO: double knock-out, cOE: conditional overexpression, KD: knock-down, OE: olfactory epithelium, oNSCs: olfactory neural stem cells, IPs: intermediate progenitors, im: immature, m: mature, OSNs: olfactory sensory neurons, OR: olfactory receptor (Slightly modified from reference#44)

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