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PMID: 11466430 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interactions between fibroblast growth factors and Notch regulate neuronal differentiation.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 15 ·2001-08-01 ·Pages 5587-96

Faux CH, Turnley AM, Epa R, Cappai R, Bartlett PF

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.

MeSH Terms
Animals Blood Proteins/pharmacology Cell Count Cell Differentiation/drug effects,physiology Cells, Cultured Down-Regulation Fibroblast Growth Factor 1 Fibroblast Growth Factor 2/metabolism,pharmacology Fibroblast Growth Factors/metabolism,pharmacology Gene Expression/drug effects Immunoglobulin Fc Fragments/genetics Intracellular Signaling Peptides and Proteins Membrane Proteins/antagonists & inhibitors,deficiency,genetics,metabolism,pharmacology Mice Mice, Inbred CBA Mice, Mutant Strains Neurons/cytology,metabolism Oligonucleotides, Antisense/pharmacology Presenilin-1 Protein Binding/physiology Proto-Oncogene Proteins/genetics,metabolism Receptor, Notch1 Receptor, Notch2 Receptor, Notch3 Receptor, Notch4 Receptors, Cell Surface/genetics,metabolism Receptors, Notch Recombinant Fusion Proteins/genetics,metabolism Signal Transduction/drug effects,physiology Stem Cells/cytology,drug effects,metabolism Transcription Factors
Chemicals
Blood Proteins Immunoglobulin Fc Fragments Intracellular Signaling Peptides and Proteins Membrane Proteins Notch1 protein, mouse Notch2 protein, mouse Notch3 protein, mouse Oligonucleotides, Antisense Presenilin-1 Proto-Oncogene Proteins Receptor, Notch1 Receptor, Notch2 Receptor, Notch3 Receptor, Notch4 Receptors, Cell Surface Receptors, Notch Recombinant Fusion Proteins Transcription Factors delta protein Fibroblast Growth Factor 2 Fibroblast Growth Factor 1 Notch4 protein, mouse Fibroblast Growth Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Faux C H
The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria 3050, Australia.
Turnley A M
Epa R
Cappai R
Bartlett P F
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-08-01
Pages
5587-96
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762663
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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