Abstract
Inductive signals and transcription factors involved in motor neuron generation have been identified, raising the question of whether these developmental insights can be used to direct stem cells to a motor neuron fate. We show that developmentally relevant signaling factors can induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo. ES cell-derived motor neurons can populate the embryonic spinal cord, extend axons, and form synapses with target muscles. Thus, inductive signals involved in normal pathways of neurogenesis can direct ES cells to form specific classes of CNS neurons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Body Patterning / drug effects
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Body Patterning / physiology
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Cell Communication / physiology
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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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Chick Embryo
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Embryonic Induction / drug effects
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Embryonic Induction / physiology*
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Graft Survival / physiology
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Green Fluorescent Proteins
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Hedgehog Proteins
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Homeodomain Proteins / metabolism
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Indicators and Reagents
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Luminescent Proteins
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Mice
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Mice, Transgenic
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Motor Neurons / cytology
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Motor Neurons / drug effects
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Motor Neurons / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Spheroids, Cellular / cytology
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Spheroids, Cellular / drug effects
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Spheroids, Cellular / metabolism
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Spinal Cord / cytology
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Spinal Cord / embryology*
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Spinal Cord / metabolism
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / metabolism*
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Trans-Activators / agonists
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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Tretinoin / pharmacology
Substances
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Hedgehog Proteins
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Homeodomain Proteins
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Indicators and Reagents
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Luminescent Proteins
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Trans-Activators
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Transcription Factors
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Hb9 protein, mouse
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Green Fluorescent Proteins
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Tretinoin