Abstract
A mechanism by which members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor cytokine family regulate gliogenesis in the developing mammalian central nervous system was characterized. Activation of the CNTF receptor promoted differentiation of cerebral cortical precursor cells into astrocytes and inhibited differentiation of cortical precursors along a neuronal lineage. Although CNTF stimulated both the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Ras-mitogen-activated protein kinase signaling pathways in cortical precursor cells, the JAK-STAT signaling pathway selectively enhanced differentiation of these precursors along a glial lineage. These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / metabolism
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Astrocytes / cytology*
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Astrocytes / drug effects
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Astrocytes / metabolism
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Cell Differentiation
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Cell Division
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Cell Lineage
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Cells, Cultured
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Cerebral Cortex / cytology*
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Cerebral Cortex / embryology
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Ciliary Neurotrophic Factor
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Cytokine Receptor gp130
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DNA-Binding Proteins / metabolism*
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Dimerization
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Glial Fibrillary Acidic Protein / biosynthesis
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Growth Inhibitors / metabolism
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Growth Inhibitors / pharmacology
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Interleukin-6*
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Janus Kinase 1
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Lymphokines / metabolism
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Lymphokines / pharmacology
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Membrane Glycoproteins / metabolism
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Nerve Growth Factors / pharmacology
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / pharmacology
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Platelet-Derived Growth Factor / pharmacology
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Protein-Tyrosine Kinases / metabolism*
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Rats
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptor, Ciliary Neurotrophic Factor
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Receptors, Cytokine / metabolism
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Receptors, Nerve Growth Factor / metabolism
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Receptors, OSM-LIF
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STAT1 Transcription Factor
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STAT3 Transcription Factor
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Signal Transduction*
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Stem Cells / cytology
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Trans-Activators / metabolism*
Substances
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Antigens, CD
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Ciliary Neurotrophic Factor
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DNA-Binding Proteins
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Glial Fibrillary Acidic Protein
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Growth Inhibitors
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Il6st protein, rat
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Interleukin-6
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Lifr protein, rat
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Lymphokines
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Membrane Glycoproteins
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Nerve Growth Factors
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Nerve Tissue Proteins
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Platelet-Derived Growth Factor
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Receptor, Ciliary Neurotrophic Factor
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Receptors, Cytokine
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Receptors, Nerve Growth Factor
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Receptors, OSM-LIF
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STAT1 Transcription Factor
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STAT3 Transcription Factor
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Stat3 protein, rat
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Trans-Activators
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Cytokine Receptor gp130
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Protein-Tyrosine Kinases
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Receptor Protein-Tyrosine Kinases
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Jak1 protein, rat
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Janus Kinase 1