Growth factor regulation of neurogenesis in adult olfactory epithelium.

Neurogenesis continues throughout adult life in the mammalian olfactory epithelium. This process is a dynamic state of proliferation, differentiation and cell death, probably regulated by autocrine and paracrine signals such as peptide growth factors. Previous investigations have demonstrated roles for some growth factors in olfactory neurogenesis in vitro, but the assay systems used make it difficult to be certain of their effects (proliferation, differentiation, enhanced survival) or their target cells. The present study investigated the effects of growth factors in cultures of purified olfactory epithelium comprising only basal cells and supporting cells in serum-free media. The advantage of this culture system is that proliferation, differentiation and survival of the basal cells and neurons can be examined separately. Under these conditions, three growth factors exerted well-defined effects: (i) fibroblast growth factor-2 stimulated proliferation of the globose basal cells; (ii) transforming growth factor-beta2 induced these cells to differentiate into neurons; and (iii) platelet-derived growth factor promoted survival of the differentiated neurons. We conclude that fibroblast growth factor-2, transforming growth factor-beta2 and platelet-derived growth factor act sequentially on precursor cells and immature neurons during neurogenesis in the adult olfactory epithelium.