Abstract
During early development in vertebrates, Sonic hedgehog (Shh) is produced by the notochord and the floor plate. A ventrodorsal gradient of Shh directs ventrodorsal patterning of the neural tube. However, Shh is also required for the survival of neuroepithelial cells. We show that Patched (Ptc) induces apoptotic cell death unless its ligand Shh is present to block the signal. Moreover, the blockade of Ptc-induced cell death partly rescues the chick spinal cord defect provoked by Shh deprivation. Thus, the proapoptotic activity of unbound Ptc and the positive effect of Shh-bound Ptc on cell differentiation probably cooperate to achieve the appropriate spinal cord development.
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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Apoptosis*
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Caspase 3
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Caspases / metabolism
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Cell Differentiation
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Cell Line
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Central Nervous System / cytology
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Central Nervous System / embryology*
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Central Nervous System / metabolism
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Chick Embryo
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Electroporation
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Epithelial Cells / cytology
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Epithelial Cells / metabolism
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Hedgehog Proteins
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Humans
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mutation
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Patched Receptors
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Patched-1 Receptor
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Protein Binding
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Protein Structure, Tertiary
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Rats
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Receptors, Cell Surface
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Signal Transduction
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Spinal Cord / cytology
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Spinal Cord / embryology
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transfection
Substances
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Hedgehog Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Patched Receptors
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Patched-1 Receptor
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Ptch1 protein, mouse
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Receptors, Cell Surface
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SHH protein, human
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Trans-Activators
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CASP3 protein, human
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Casp3 protein, mouse
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Casp3 protein, rat
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Caspase 3
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Caspases