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Previous Article | Next Article
The Journal of Neuroscience, August 1, 2001, 21(15):5587-5596
Interactions between Fibroblast Growth Factors and Notch Regulate Neuronal Differentiation
Clare H. Faux1, Ann M. Turnley1, Ruwan Epa2, Roberto Cappai3, and Perry F. Bartlett1 1 The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria 3050, Australia, and Departments of 2 Physiology and 3 Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
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.
Key words: Notch; Delta; growth factors; fibroblast growth factor (FGF); neuroepithelial precursor cells; regulation of differentiation
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155587-10$05.00/0
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