Basic fibroblast growth factor supports human olfactory neurogenesis by autocrine/paracrine mechanisms.
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.
Pediatric Oncology Branch, NCI, NIH, Bethesda, Maryland, USA.
F
F
Ensoli
V
V
Fiorelli
B
B
Vannelli
T
T
Barni
M
M
De Cristofaro
B
B
Ensoli
C J
CJ
Thiele
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000294:innervation*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D006133:Growth Substances; D009414:Nerve Growth Factors; D016376:Oligonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004247:DNA