Growth Factor Expression Associated With Regulation of Olfactory Neurogenesis

Abstract

Olfactory neurons arise from the division of a stem cell in the basal area of the epithelium. After dividing asymmetrically and symmetrically, the stem cell gives rise to many immature olfactory receptor neurons that gradually differentiate into mature neurons as they migrate away from the basement membrane. The neurogenesis in the olfactory epithelium takes place throughout adult life, which makes the olfactory epithelium system a useful model with which to study the mechanisms that direct neural development. Olfactory neurogenesis is highly regulated for the need of maintaining the equilibrium between the basal cell mitosis, cell death and cell survival in olfactory epithelium, for which many growth factors have been reported to play roles in regulating olfactory neurogenesis. Many reports observed the proliferative role of TGF and EGF in the olfactory neurogenesis and the expression of their receptors in horizontal basal cells, suggesting their signaling pathways for proliferation were mediated by a common receptor on the horizontal basal cells. FGF2 was reported to induce proliferation in a mouse embryo explant, a basal cell line, and in our laboratory, a basal cell culture. However, the target cells of FGF2 in the olfactory epithelium were not clear at the time of the research. TGF -2 was observed to stimulate differentiation in semi-dissociated olfactory tissues, in basal cell cultures and a basal cell line. Some of the receptors for TGF growth factors were found to be expressed in the olfactory epithelium but the identity of the target cells of TGF growth factors and the cells expressing them remained largely unknown. PDGF was observed in our laboratory to promote survival of immature neurons but there was no evidence to show the existence of its receptors on the immature neurons or to locate its source in the olfactory epithelium. This project aimed to identify and characterize the cells expressing TGF -2, PDGF and FGF growth factors and receptors in the olfactory epithelium using techniques of RT-PCR, immunohistochemistry, and in situ hybridisation. Our results have shown most members of TGF -2 superfamily were expressed in the olfactory epithelium in that TGF growth factors 1, 2, 3 and TGF receptor type 1, 2 and 3 were expressed extensively in superficially located basal cells, immature and mature neurons. FGF1 was expressed in olfactory epithelium. FGF2 and FGFr-1 were expressed by neurons and presumed globose basal cells. The supporting cells were like to express FGF2 mRNA. PDGF A and PDGF receptor had similar expression patterns in the olfactory epithelium. In support of previous studies, this project has provided in vivo evidence for the cells expressing the growth factors of importance and for the target cells these growth factors might act on. In addition to these, this project also investigated an unknown gene, 16b5, which was previously found to be unregulated by differentiation of an olfactory cell line, and has provided the in vivo evidence to support the finding.