Interactions between fibroblast growth factors and Notch regulate neuronal differentiation

Faux, CH, Turnley, AM, Epa, R, Cappai, R and Bartlett, PF (2001) Interactions between fibroblast growth factors and Notch regulate neuronal differentiation. Journal of Neuroscience, 21 15: 5587-5596.

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Author Faux, CH
Turnley, AM
Epa, R
Cappai, R
Bartlett, PF
Title Interactions between fibroblast growth factors and Notch regulate neuronal differentiation
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2001
Sub-type Article (original research)
Open Access Status File (Publisher version)
Volume 21
Issue 15
Start page 5587
End page 5596
Total pages 10
Place of publication Washington
Publisher Soc Neuroscience
Language eng
Abstract The differentiation of precursor cells into neurons has been shown to be influenced by both the Notch signaling pathway and growth factor stimulation. In this study, the regulation of neuronal differentiation by these mechanisms was examined in the embryonic day 10 neuroepithelial precursor (NEP) population. By downregulating Notch1 expression and by the addition of a Delta1 fusion protein (Delta Fc), it was shown that signaling via the Notch pathway inhibited neuron differentiation in the NEP cells, in vitro. The expression of two of the Notch receptor homologs, Notch1 and Notch3, and the ligand Delta1 in these NEP cells was found to be influenced by a number of different growth factors, indicating a potential interaction between growth factors and Notch signaling. Interestingly, none of the growth factors examined promoted neuron differentiation; however, the fibroblast growth factors (FGFs) 1 and 2 potently inhibited differentiation. FGF1 and FGF2 upregulated the expression of Notch and decreased expression of Delta1 in the NEP cells. In addition, the inhibitory response of the cells to the FGFs could be overcome by downregulating Notch1 expression and by disrupting Notch cleavage and signaling by the ablation of the Presenilin1 gene. These results indicate that FGF1 and FGF2 act via the Notch pathway, either directly or indirectly, to inhibit differentiation. Thus, signaling through the Notch receptor may be a common regulator of neuronal differentiation within the developing forebrain.
Keyword Neurosciences
growth factors
fibroblast growth factor (FGF)
neuroepithelial precursor cells
regulation of differentiation
Neurogenic Gene-delta
Intracellular Domain
Transcription Factor
Proteolytic Release
Xenopus Embryos
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 82 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 17 Oct 2007, 10:44:42 EST