Abstract
There is growing evidence that sonic hedgehog (Shh) signaling regulates ventral neuronal fate in the vertebrate central nervous system through Nkx-class homeodomain proteins. We have examined the patterns of neurogenesis in mice carrying a targeted mutation in Nkx6.1. These mutants show a dorsal-to-ventral switch in the identity of progenitors and in the fate of postmitotic neurons. At many axial levels there is a complete block in the generation of V2 interneurons and motor neurons and a compensatory ventral expansion in the domain of generation of V1 neurons, demonstrating the essential functions of Nkx6.1 in regional patterning and neuronal fate determination.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Cell Lineage
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Cells, Cultured
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DNA-Binding Proteins / biosynthesis
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Gene Targeting
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Hedgehog Proteins
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / physiology*
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Immunohistochemistry
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In Situ Hybridization
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LIM-Homeodomain Proteins
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Mice
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Motor Neurons / metabolism*
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Mutagenesis, Site-Directed
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Nerve Tissue Proteins*
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PAX2 Transcription Factor
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Protein Biosynthesis
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Repressor Proteins / biosynthesis
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Signal Transduction
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Spinal Cord / embryology
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Stem Cells / metabolism
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Time Factors
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Tissue Distribution
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Trans-Activators*
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Transcription Factors / biosynthesis
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Hedgehog Proteins
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Homeodomain Proteins
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ISL2 protein, human
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Isl-2 protein, vertebrate
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Isl2 protein, mouse
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LIM-Homeodomain Proteins
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Lhx3 protein
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Nerve Tissue Proteins
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Nkx6-1 protein, mouse
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PAX2 Transcription Factor
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Pax2 protein, mouse
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Repressor Proteins
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SHH protein, human
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SIM1 protein, human
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Sim1 protein, mouse
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Trans-Activators
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Transcription Factors
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VSX2 protein, human
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Vsx2 protein, mouse
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insulin gene enhancer binding protein Isl-1