title: Role of Sonic Hedgehog Signaling in Oligodendrocyte Differentiation.
abstract: During development, the secreted molecule Sonic Hedgehog (Shh) is required for lineage specification and proliferation of oligodendrocyte progenitors (OLPs), which are the glia cells responsible for the myelination of axons in the central nervous system (CNS). Shh signaling has been implicated in controlling both the generation of oligodendrocytes (OLGs) during embryonic development and their production in adulthood. Although, some evidence points to a role of Shh signaling in OLG development, its involvement in OLG differentiation remains to be fully determined. The objective of this study was to assess whether Shh signaling is involved in OLG differentiation after neural stem cell commitment to the OLG lineage. To address these questions, we manipulated Shh signaling using cyclopamine, a potent inhibitor of Shh signaling activator Smoothened (Smo), alone or combined with the agonist SAG in OLG primary cultures and assessed expression of myelin-specific markers. We found that inactivation of Shh signaling caused a dose-dependent decrease in myelin basic protein (MBP) and myelin associated glycoprotein (MAG) in differentiating OLGs. Co-treatment of the cells with SAG reversed the inhibitory effect of cyclopamine on both myelin-specific protein levels and morphological changes associated with it. Further experiments are required to elucidate the molecular mechanism by which Shh signaling regulates OLG differentiation.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, H3G 1Y6, Canada.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, H3G 1Y6, Canada. guillermina.almazan@mcgill.ca.
authors.forename: Guillermina
authors.identifier: http://orcid.org/0000-0003-3605-9082
authors.initials: G
authors.lastname: Almazan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D053823:Hedgehog Proteins / Q000502:physiology*; D004676:Myelin Basic Protein / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000072086:Smoothened Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; D004676:Myelin Basic Protein; D018992:Myelin-Associated Glycoprotein; C546888:Shh protein, rat; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids; C000541:cyclopamine
keywords: Cyclopamine; Lineage specification; SAG; Shh; Smoothened