Elsevier

Neuroscience

Volume 86, Issue 3, 8 June 1998, Pages 881-893
Neuroscience

Basic fibroblast growth factor supports human olfactory neurogenesis by autocrine/paracrine mechanisms

https://doi.org/10.1016/S0306-4522(98)00104-3Get rights and content

Abstract

Throughout life, olfactory sensory neurons are renewed from a population of dividing stem cells. Little is known about the molecular mechanisms that regulate the activation, self-renewal and differentiation of olfactory neuronal precursors; however, evidence indicates that soluble mediators may play a central role in olfactory neurogenesis. To identify molecules that regulate olfactory self-renewal and differentiation, we have recently established, cloned and propagated in vitro primary long-term cell cultures from the human fetal olfactory neuroepithelium. Here, we show that primary human olfactory neuroblasts synthesize and release biologically active basic fibroblast growth factor which, in turn, supports neuroblast growth by autocrine/paracrine mechanisms. The growth-promoting activity of basic fibroblast growth factor is dose dependent, and is accompanied by morphological changes of the cells and by an increase in the expression of neuronal-related genes.

These observations indicate that endogenous basic fibroblast growth factor participates in controlling olfactory self-renewal and suggest that this cytokine represents a key regulatory element of olfactory neurogenesis.

Section snippets

Cell cultures

The primary human olfactory neuroblast long-term cell cultures FNC-B4 and FNC-A6 were isolated, cloned and propagated in vitro from human fetal olfactory neuroepithelium, as described previously.[60]These cells express neuronal markers as well as olfactory-associated proteins,36, 60indicating that they originate from the neuroblastic stem cell compartment, which gives rise to mature olfactory neurons throughout life. These cells were cultured in Coon's modification of F12 medium supplemented

Basic fibroblast growth factor increases primary human olfactory neuroblast proliferation in a dose-dependent manner

Olfactory receptor neurons undergo a continual process of neurogenesis, which includes the activation, self-renewal and maturation of neuronal precursors.8, 9, 22, 23, 24The molecular mechanisms involved in this process are not fully understood; however, evidence suggests that different polypeptide growth factors may play a crucial role in these events.12, 38, 51We have recently established long-term cell cultures of primary human olfactory neuroblasts which have been isolated, cloned and

Discussion

To determine the role of extracellular signals in regulating olfactory neurogenesis, we have examined the effects of peptide growth factors on the proliferation and differentiation of primary human olfactory neuroblasts. We show that proliferation of olfactory precursor cells is positively controlled by endogenous bFGF production, which leads to an expansion of these cells accompanied by structural modifications and increased expression of tissue-specific genes. However, the transition of

Conclusions

In summary, our data indicate that bFGF plays a prominent role in supporting olfactory self-renewal. The cytokine is produced endogenously by olfactory neuroblasts and released in a bioactive form which can promote autocrine/paracrine growth of olfactory precursors. Thus, endogenous bFGF production by olfactory neuronal precursors may represent a key element in olfactory neurogenesis, and may play a major role in the development and plasticity of the human olfactory system.

Unlinked reference

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Acknowledgements

This work was partially supported by ANLAIDS and MURST (50% and 60%) and by Regione Toscana (III° Programma di Ricerca Sanitaria Finalizzata, no. 250 /c).

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