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 v i v aThese 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.

Progenitor cells of the olfactory receptor neuron lineage

“…Interestingly, in Mash1 Ϫ/Ϫ mice, neurogenesis is halted and Ngn1 fails to be expressed (Cau et al, 1997). These findings, taken together with other studies showing that neuronal progenitors undergo apoptosis in Mash1 Ϫ/Ϫ OE (Calof et al, 1996a), indicate that INPs are not produced when MASH1 is absent and suggest that Ngn1 is a marker for INPs. In addition to Ngn1, several other molecular markers for INPs have been proposed.…”

“…Neuronal colony forming cell (Mumm et al, 1996) GBC Hes1* (Cau et al, 2000) BF-1* (Hatini et al, 1999;Yao et al, 2001) Mash1ϩ progenitor (Gordon et al, 1995) GBC Mash1 (Cau et al, 1997;Gordon et al, 1995) OAZ* (Tsai and Reed, 1997) BF-1* (Hatini et al, 1999); Fig. 3B (this paper) Otx-2* (Calof et al, 1996a;Simeone et al, 1993) Hes1* (Cau et al, 2000) INP (Calof and Chikaraishi, 1989) GBC Ngn1 (Cau et al, 1997); Fig. 3A (this paper) OAZ* (Tsai and Reed, 1997) BF-1* (Hatini et al, 1999); Fig.…”

“…3A (this paper) OAZ* (Tsai and Reed, 1997) BF-1* (Hatini et al, 1999); Fig. 3b (this paper) Otx-2* (Calof et al, 1996a;Simeone et al, 1993) Hes1*, Hes5* (Cau et al, 2000) ORN (Calof and Chikaraishi, 1989) ORN NCAM, GAP43 (Calof and Chikaraishi, 1989;Verhaagen et al, 1989) OMP (Farbman and Margolis, 1980); Fig. 14 (this paper) NeuroD (Cau et al, 1997) Class III ␤-tubulin, SCG10 Olf-1 (Wang and Reed, 1993) Peripherin (Gorham et al, 1991) Stathmin (Camoletto et al, 2001) In order to examine the properties of the neuronal stem cell in more detail, we designed experiments to purify neuronal progenitor cells and characterize their development in vitro. To accomplish this, the neuronal cell fraction was prepared from embryonic OE and neuronal progenitors purified from it using anti-NCAM antibodies to remove NCAM-expressing ORNs (Mumm et al, 1996).…”

Manipulation of Neural Precursors in situ Induction of Neurogenesis in the Neocortex of Adult Mice

“…Olfactory nerve lesions or olfactory bulb lesions, which lead to the degeneration of axotomized neurons (Graziadei and Graziadei 1979;Carr and Farbman 1992), result in an increase in proliferation of precursors (Caggiano et al 1994;Graziadei and Graziadei 1979;Carr and Farbman 1992;Calof et al 1996;Samanen and Forbes 1984). The new neurons that form in the adult olfactory epithelium send axons through the olfactory nerve and into the mature olfactory bulb (Barber 1982;Crews and Hunter 1994).…”

Serine protease inhibitor Spi2 mediated apoptosis of olfactory neurons

“…Olfactory neurons are known to have a limited lifespan (3 ± 4 weeks) and die through apoptosis spontaneously. 2,3,6 These neurons are renewed by permanent neurogenesis from local neuronal progenitors. 7 Surgical ablation of their unique target, the olfactory bulb (Figure 1), was shown to trigger massive and synchronous apoptotic death of olfactory neurons, culminating 36 h after lesion.…”