Abstract
Olfactory receptor neurons are produced continuously in mammalian olfactory epithelium in vivo, but in explant cultures neurogenesis ceases abruptly. We show that in vitro neurogenesis is prolonged by fibroblast growth factors (FGFs), which act in two ways. FGFs increase the likelihood that immediate neuronal precursors (INPs) divide twice, rather than once, before generating neurons; this action requires exposure of INPs to FGFs by early G1. FGFs also cause a distinct subpopulation of explants to generate large numbers of neurons continually for at least several days. The data suggest that FGFs delay differentiation of a committed neuronal transit amplifying cell (the INP) and support proliferation or survival of a rare cell, possibly a stem cell, that acts as a progenitor to INPs.
Highlights
The mammalian olfactoryepithelium (OE) is uniquely suited to studies of how neurogenesis is controlled.In the OE, proliferation of neuronal precursor cells and differentiation of their progeny into olfactory receptor neurons (ORNs) begin during embryogenesis and continue throughout life (Graziadei and MontiGraziadei, 1978)
FGF4 and FGF7 were each tested at 1 and 100 rig/ml and gave effects similar to those observed at 10 nglml [data not shown])
Proliferation factors were calculated as follows: for each explant, the explant labeling index was calculated as the number of migratory cells with silver grains over their nuclei divided by the area of the explant
Summary
The mammalian olfactoryepithelium (OE) is uniquely suited to studies of how neurogenesis is controlled.In the OE, proliferation of neuronal precursor cells and differentiation of their progeny into olfactory receptor neurons (ORNs) begin during embryogenesis and continue throughout life (Graziadei and MontiGraziadei, 1978). The mammalian olfactoryepithelium (OE) is uniquely suited to studies of how neurogenesis is controlled. In the OE, proliferation of neuronal precursor cells and differentiation of their progeny into olfactory receptor neurons (ORNs) begin during embryogenesis and continue throughout life Even in adults, these processes appear to be regulated, since in vivo manipulations that lead todeath of ORNs result in increased mitotic activityof neuronal precursors We previously developed an explant culture system for purified embryonic mouse OE to study neurogenesis under defined conditions. Three major cell types are present in these cultures: basal cells, which express keratins; postmitotic. ORNs, which express the neural cell adhesion molecule N-CAM; and a third cell type, which expresses neither keratins nor N-CAM (Calof and Chikaraishi, 1989).
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