Abstract
We show that Schwann cell-derived Desert hedgehog (Dhh) signals the formation of the connective tissue sheath around peripheral nerves. mRNAs for dhh and its receptor patched (ptc) are expressed in Schwann cells and perineural mesenchyme, respectively. In dhh-/- mice, epineurial collagen is reduced, while the perineurium is thin and disorganized, has patchy basal lamina, and fails to express connexin 43. Perineurial tight junctions are abnormal and allow the passage of proteins and neutrophils. In nerve fibroblasts, Dhh upregulates ptc and hedgehog-interacting protein (hip). These experiments reveal a novel developmental signaling pathway between glia and mesenchymal connective tissue and demonstrate its molecular identity in peripheral nerve. They also show that Schwann cell-derived signals can act as important regulators of nerve development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Collagen / metabolism
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Connective Tissue / growth & development*
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Connective Tissue / ultrastructure
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Connexin 43 / biosynthesis
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Connexin 43 / genetics
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Hedgehog Proteins
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Immunohistochemistry
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In Situ Hybridization
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Proteins / biosynthesis*
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Membrane Proteins / genetics
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Mice
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Mice, Knockout
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Microscopy, Electron
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Neuroglia / physiology
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Patched Receptors
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Patched-1 Receptor
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Peripheral Nerves / growth & development*
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Peripheral Nerves / metabolism
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Peripheral Nerves / ultrastructure
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Protein Biosynthesis*
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Proteins / genetics
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Receptors, Cell Surface
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Reverse Transcriptase Polymerase Chain Reaction
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Schwann Cells / physiology*
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Schwann Cells / ultrastructure
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Signal Transduction / genetics
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Signal Transduction / physiology
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Trans-Activators*
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Up-Regulation / genetics
Substances
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Carrier Proteins
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Connexin 43
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Hedgehog Proteins
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Hhip protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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Membrane Proteins
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Patched Receptors
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Patched-1 Receptor
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Proteins
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Ptch1 protein, mouse
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RNA, Messenger
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Receptors, Cell Surface
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Trans-Activators
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Collagen