Abstract
Knowledge about signaling pathways in response to external signals is needed to understand the regulation of stem cell proliferation and differentiation toward particular cell fates. The Ras/extracellular signal-regulated kinase (ERK) pathway has been suggested to play an essential role in neuronal differentiation. We have examined ERK signaling in the transition from multipotent stem cell to post-mitotic progeny using primary stem cells from the rat embryonic cortex. Fibroblast growth factor-2 (FGF-2) is a stem cell mitogen, whereas platelet-derived growth factor AA (PDGF-AA) expands a pool of committed neuronal precursors from stem cells. When comparing ERK activation by these growth factors, we found that FGF-2 stimulates high and PDGF-AA lower levels of ERK phosphorylation in stem cells. Differentiation was monitored as down-regulation of the bHLH transcription factor mammalian achaete-scute homologue-1 (MASH1). Even in the absence of active ERK, MASH1 became down-regulated and microtubule-associated protein 2-positive cells could form. Thus, ERK activation seems dispensable for the earliest steps of CNS stem cell differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Blotting, Western
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Brain / embryology
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Bromodeoxyuridine / pharmacology
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Cell Differentiation
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Central Nervous System / cytology*
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DNA-Binding Proteins / metabolism
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Detergents / pharmacology
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Down-Regulation
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Enzyme Activation
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Fibroblast Growth Factor 2 / metabolism*
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Immunohistochemistry
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Microtubule-Associated Proteins / metabolism
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism*
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Neurons / metabolism*
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Octoxynol / pharmacology
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Phosphorylation
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Platelet-Derived Growth Factor / metabolism*
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Rats
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Rats, Sprague-Dawley
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Signal Transduction*
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Time Factors
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Transcription Factors / metabolism
Substances
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Ascl1 protein, rat
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Detergents
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Microtubule-Associated Proteins
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Platelet-Derived Growth Factor
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Transcription Factors
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platelet-derived growth factor A
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Fibroblast Growth Factor 2
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Octoxynol
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Bromodeoxyuridine