Abstract
Sonic Hedgehog (Shh) is a secreted protein that controls cell fate and mitogenesis in the developing nervous system. Here we show that a constitutively active form of Smoothened (Smo-M2) mimics concentration-dependent actions of Shh in the developing neural tube, including activation of ventral marker genes (HNF3beta, patched, Nkx2.2, netrin-1), suppression of dorsal markers (Pax-3, Gli-3, Ephrin A5) and induction of ventral neurons (dopaminergic, serotonergic) and ventrolateral motor neurons (Islet-1+, Islet-2+, HB9+) and interneurons (Engrailed-1+, CHX10+). Furthermore, Smo-M2's patterning activities were cell autonomous, occurring exclusively in cells expressing Smo-M2. These findings suggest that Smo is a key signaling component in the Hh receptor and that Shh patterns the vertebrate nervous system as a morphogen, rather than through secondary relay signals.
MeSH terms
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Amino Acid Substitution
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Animals
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Antigens, Differentiation / metabolism
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Body Patterning / genetics
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Body Patterning / physiology*
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Brain / cytology
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Brain / embryology
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Brain / metabolism
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Chick Embryo
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Embryo, Mammalian
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Embryonic Induction*
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Gene Expression Regulation, Developmental
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Genes, Reporter
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Hedgehog Proteins
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Homeobox Protein Nkx-2.2
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Interneurons / cytology
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Interneurons / metabolism
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Mice
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Mice, Transgenic
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Motor Neurons / cytology
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Motor Neurons / metabolism
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Neural Crest / cytology
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Neural Crest / embryology*
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Neural Crest / metabolism
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Proteins / physiology
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Receptors, Cell Surface / physiology*
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Receptors, G-Protein-Coupled*
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Signal Transduction / genetics
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Signal Transduction / physiology*
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Smoothened Receptor
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Spinal Cord / cytology
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Spinal Cord / embryology
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Trans-Activators*
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Transfection
Substances
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Antigens, Differentiation
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Hedgehog Proteins
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Homeobox Protein Nkx-2.2
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Nkx2-2 protein, mouse
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Proteins
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Smo protein, mouse
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Smoothened Receptor
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Trans-Activators