Neurogenesis and cell death in olfactory epithelium

Abstract

The olfactory epithelium (OE) of the mammal is uniquely suited as a model system for studying how neurogenesis and cell death interact to regulate neuron number during development and regeneration. To identify factors regulating neurogenesis and neuronal death in the OE, and to determine the mechanisms by which these factors act, investigators studied OE using two major experimental paradigms: tissue culture of OE; and ablation of the olfactory bulb or severing the olfactory nerve in adult animals, procedures that induce cell death and a subsequent surge of neurogenesis in the OE in vivo. These studies characterized the cellular stages in the olfactory receptor neuron (ORN) lineage, leading to the realization that at least three distinct stages of proliferating neuronal precursor cells are employed in generating ORNs. The identification of a number of factors that act to regulate proliferation and survival of ORNs and their precursors suggests that these multiple developmental stages may serve as control points at which cell number is regulated by extrinsic factors. In vivo surgical studies, which have shown that all cell types in the neuronal lineage of the OE undergo apoptotic cell death, support this idea. These studies, and the possible coregulation of neuronal birth and apoptosis in the OE, are discussed.

Fine structural aspects of apoptosis in the olfactory epithelium

“…TUNEL-positive cells decreased in number and reached the control level 5 days after bulbectomy (Holcomb et al, 1995). the same time a peak loss of ORNs as measured by epithelial thickness was observed in the septal OE (Calof et al, 1996). Using scanning electron microscopy, almost a total absence of ORNs in the hamster OE was found 4 days after bulbectomy (Morrison & Costanzo, 1989).…”

Activation of purinergic receptors induces proliferation and neuronal differentiation in Swiss Webster mouse olfactory epithelium

“…The idea that cell death may be necessary to induce new cell production is supported by studies that have found increased neurogenesis after targeted apoptosis (Calof et al, 1996). A number of specific local molecular cues or cell-autonomous factors are candidates for mediating injury-induced increases in proliferating basal cells.…”

Subventricular zone-derived, newly generated neurons populate several olfactory and limbic forebrain regions

“…In rodents, lagomorphs and non-human primates, olfaction is still one of the predominant senses. The fact that the neural epithelium in the nasal mucosa consists of a local pool of constantly regenerating neurons [31] may provide a clue as to why neurogenesis occurs in brain structures that are part of the olfactory system. The axons from the continually regenerating olfactory receptor cells project to the olfactory bulb, where a robust pool of newly generated neurons occurs that is derived from the SVZ via the RMS [5].…”