Abstract
Chondroitin sulfates (CSs) and dermatan sulfates (DSs) are enriched in the microenvironment of neural stem cells (NSCs) during development and in the adult neurogenic niche, and have been implicated in mechanisms governing neural precursor migration, proliferation and differentiation. In contrast to previous studies, in which a chondroitinaseABC-dependent unselective deglycosylation of both CSs and DSs was performed, we used chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1)- and dermatan 4-O-sulfotransferase-1 (Chst14/D4st1)-deficient NSCs specific for CSs and DSs, respectively, to investigate the involvement of specific sulfation profiles of CS and DS chains, and thus the potentially distinct roles of CSs and DSs in NSC biology. In comparison to wild-type controls, deficiency for Chst14 resulted in decreased neurogenesis and diminished proliferation of NSCs accompanied by increased expression of GLAST and decreased expression of Mash-1, and an upregulation of the expression of the receptors for fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF). By contrast, deficiency in Chst11 did not influence NSC proliferation, migration or differentiation. These observations indicate for the first time that CSs and DSs play distinct roles in the self-renewal and differentiation of NSCs.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Apoptosis
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Bromodeoxyuridine / administration & dosage
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Bromodeoxyuridine / pharmacology
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Cell Differentiation
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Cell Movement
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Cell Proliferation*
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Embryo, Mammalian / cytology
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Embryo, Mammalian / drug effects
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Embryo, Mammalian / metabolism
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ErbB Receptors / genetics
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ErbB Receptors / metabolism
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Excitatory Amino Acid Transporter 1 / genetics
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Excitatory Amino Acid Transporter 1 / metabolism
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Gene Expression Regulation, Enzymologic
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Immunohistochemistry
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Mice
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Mice, Inbred C57BL
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Neural Stem Cells / cytology
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Neural Stem Cells / drug effects
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Neural Stem Cells / enzymology*
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Neurogenesis
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Receptor, Fibroblast Growth Factor, Type 2 / genetics
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Receptor, Fibroblast Growth Factor, Type 2 / metabolism
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Stem Cell Niche
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Sulfotransferases / genetics
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Sulfotransferases / metabolism*
Substances
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Ascl1 protein, mouse
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Basic Helix-Loop-Helix Transcription Factors
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Excitatory Amino Acid Transporter 1
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Slc1a3 protein, mouse
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EGFR protein, mouse
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ErbB Receptors
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Fgfr2 protein, mouse
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Receptor, Fibroblast Growth Factor, Type 2
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Chst11 protein, mouse
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Sulfotransferases
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dermatan-4-sulfotransferase-1
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Bromodeoxyuridine