Transcriptional regulatory network during development in the olfactory epithelium

Abstract

Regeneration, a process of reconstitution of the entire tissue, occurs throughout life in the olfactory epithelium (OE). Regeneration of OE consists of several stages: proliferation of progenitors, cell fate determination between neuronal and non-neuronal lineages, their differentiation and maturation. How the differentiated cell types that comprise the OE are regenerated, is one of the central questions in olfactory developmental neurobiology. The past decade has witnessed considerable progress regarding the regulation of transcription factors (TFs) involved in the remarkable regenerative potential of OE. Here, we review current state of knowledge of the transcriptional regulatory networks that are powerful modulators of the acquisition and maintenance of developmental stages during regeneration in the OE. Advance in our understanding of regeneration will not only shed light on the basic principles of adult plasticity of cell identity, but may also lead to new approaches for using stem cells and reprogramming after injury or degenerative neurological diseases.

Fig. 1.. Structure of olfactory epithelium (OE).

(A) Sagittal plane of the rodent nose elucidating the location of the olfactory epithelium (red). (B) The olfactory epithelium is composed of several cell types from apical to basal layers: supporting cells (SCs), immature and mature olfactory receptor neurons (ORNs), and globose and horizontal basal cells (GBCs and HBCs). LP: lamina propria.

Fig. 2.. Process of regeneration in the OE.

The OE retains active processes for supplying new ORNs and supporting cells during regeneration. These cell types can be distinguished by several markers. (A) During ongoing ORNs generation, HBCs and act as olfactory stem cells for other cells in the OE. After neuronal cell fate determination of GBCs, they differentiate and maturate into ORNs. (B) In the non-neuronal lineage of the OE, supporting cells are generated from HBCs, but detailed process is under investigation. GBCt: transit amplifying globose basal cell, GBCinp: immediate neuronal precursor globose basal cell, ORNi: immature olfactory receptor neuron, ORNm: mature olfactory receptor neuron, ICAM1: Intercellular Adhesion Molecule 1, GAP43: 43kDa growth associated protein, NCAM: neural cell adhesion molecule, NST: neuron specific tubulin, OMP: olfactory marker protein, SUS4: sucrose synthase 4, Reep6: Receptor Accessory Protein 6, K18: keratin 18.

Fig. 3.. Scheme of transcriptional regulatory network during regeneration in the OE.

Sox2, Pax6 and p63 regulate proliferation and differentiation of multipotent progenitor cells. Two representative bHLH TFs, Mash1 and Hes1 might have role in the determination of cell fate between neuronal and non-neuronal lineages. And their multiple component of the downstream get involved in differentiation and final maturation of each cell fate. GBCt: transit amplifying globose basal cell, GB_Cinp: immediate neuronal precursor globose basal cell, ORNi: mmature olfactory receptor neuron, ORN_m: mature olfactory receptor neuron.