Abstract
Inhibition of bone morphogenetic protein (BMP) signaling is required for vertebrate neural induction, and fibroblast growth factors (FGFs) may affect neural induction through phosphorylation at the linker region of Smad1, thus regulating BMP signaling. Here we show that human embryonic stem cells efficiently convert to neuroepithelial cells in the absence of BMP antagonists, or even when exposed to high concentrations of exogenous BMP4. Molecular and functional analyses revealed multiple levels of endogenous BMP signaling inhibition that may account for the efficient neural differentiation. Blocking FGF signaling inhibited neural induction, but did not alter the phosphorylation of the linker region of Smad1, suggesting that FGF enhances human neural specification independently of BMP signaling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Bone Morphogenetic Protein 4 / pharmacology*
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Bone Morphogenetic Proteins / antagonists & inhibitors*
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Bone Morphogenetic Proteins / metabolism
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Carrier Proteins / pharmacology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cells, Cultured
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Embryonic Stem Cells / cytology*
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Embryonic Stem Cells / drug effects*
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Embryonic Stem Cells / metabolism
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Eye Proteins / biosynthesis
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Fibroblast Growth Factors / antagonists & inhibitors
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Fibroblast Growth Factors / metabolism*
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Fluorescent Antibody Technique
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Homeodomain Proteins / biosynthesis
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Humans
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Immunohistochemistry
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Neurons / cytology*
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Neurons / drug effects*
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Neurons / metabolism
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Octamer Transcription Factor-3 / biosynthesis
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PAX6 Transcription Factor
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Paired Box Transcription Factors / biosynthesis
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Phosphorylation
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Repressor Proteins / biosynthesis
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Signal Transduction / drug effects
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Smad1 Protein / antagonists & inhibitors
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Smad1 Protein / metabolism
Substances
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BMP4 protein, human
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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Carrier Proteins
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Eye Proteins
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Homeodomain Proteins
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Octamer Transcription Factor-3
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PAX6 Transcription Factor
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PAX6 protein, human
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POU5F1 protein, human
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Paired Box Transcription Factors
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Repressor Proteins
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SMAD1 protein, human
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Smad1 Protein
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noggin protein
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Fibroblast Growth Factors