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