Abstract
The morphogen sonic hedgehog (Shh) is implicated in neural tissue patterning and the growth of brain structures during embryogenesis and postnatal development and is also present in the adult brain. Shh signals through interaction with the tumour suppressor Patched (Ptc). This receptor for Shh is associated with Smoothened (Smo), a protein with high homology to the G-protein coupled receptors. However, little is known about the transduction mechanisms implicated in Shh signalling in the adult brain. The study described here shows that injection of aminoterminal myristoylated Shh (myrShhN) into the adult rat striatum robustly increases the levels of Ptc transcripts in selective brain areas including the subventricular zone (SVZ). The adult SVZ contains cell progenitors, which can proliferate and differentiate into new neurons and glia. In the myrShhN injected animals, proliferation and differentiation of these SVZ precursor cells were not affected as demonstrated by BrdU incorporation and immunohistochemistry performed with specific antibodies for nestin (uncommitted neural progenitors), PSA-NCAM (migrating neuroblasts) or GFAP (astrocytes). Together with the presence of Smo expressing cells and amino-terminal Shh (ShhN) protein in SVZ area of untreated animals, the data presented here supports the hypothesis that the Shh pathway may be activated in the adult brain, and that a niche for Shh signalling exists within the adult SVZ.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / metabolism
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Basic Helix-Loop-Helix Transcription Factors
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cell Division / drug effects
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Cell Division / physiology
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DNA-Binding Proteins*
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Glial Fibrillary Acidic Protein / metabolism
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Hedgehog Proteins
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Immunohistochemistry
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Intermediate Filament Proteins / metabolism
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Lateral Ventricles / cytology
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Lateral Ventricles / growth & development
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Male
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Membrane Proteins / drug effects
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Membrane Proteins / metabolism*
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Myelin Proteolipid Protein / metabolism
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Neostriatum / drug effects
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Neostriatum / growth & development*
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Neostriatum / metabolism
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Nerve Tissue Proteins / metabolism
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Nestin
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Neural Cell Adhesion Molecule L1 / metabolism
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Oligodendroglia / cytology
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Oligodendroglia / metabolism
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Patched Receptors
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Rats
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Rats, Inbred Lew
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / metabolism
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Receptors, G-Protein-Coupled*
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Sialic Acids / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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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 / metabolism*
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Trans-Activators / pharmacology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Glial Fibrillary Acidic Protein
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Hedgehog Proteins
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Intermediate Filament Proteins
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Membrane Proteins
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Myelin Proteolipid Protein
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Nerve Tissue Proteins
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Nes protein, rat
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Nestin
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Neural Cell Adhesion Molecule L1
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Olig1 protein, rat
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Patched Receptors
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Plp1 protein, rat
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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Sialic Acids
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Trans-Activators
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polysialyl neural cell adhesion molecule