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Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation

Primary Cilia (PC) are a very likely place for signal integration where multiple signaling pathways converge. Two major signaling pathways clearly shown to signal through the PC, Sonic Hedgehog (Shh) and PDGF-Rα, are particularly important for the proliferation and differentiation of oligodendrocyte...

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Autores principales: Falcón-Urrutia, Paulina, Carrasco, Carlos M., Lois, Pablo, Palma, Veronica, Roth, Alejandro D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517900/
https://www.ncbi.nlm.nih.gov/pubmed/26218245
http://dx.doi.org/10.1371/journal.pone.0133567
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author Falcón-Urrutia, Paulina
Carrasco, Carlos M.
Lois, Pablo
Palma, Veronica
Roth, Alejandro D.
author_facet Falcón-Urrutia, Paulina
Carrasco, Carlos M.
Lois, Pablo
Palma, Veronica
Roth, Alejandro D.
author_sort Falcón-Urrutia, Paulina
collection PubMed
description Primary Cilia (PC) are a very likely place for signal integration where multiple signaling pathways converge. Two major signaling pathways clearly shown to signal through the PC, Sonic Hedgehog (Shh) and PDGF-Rα, are particularly important for the proliferation and differentiation of oligodendrocytes, suggesting that their interaction occurs in or around this organelle. We identified PC in rat oligodendrocyte precursor cells (OPCs) and found that, while easily detectable in early OPCs, PC are lost as these cells progress to terminal differentiation. We confirmed the interaction between these pathways, as cyclopamine inhibition of Hedgehog function impairs both PDGF-mediated OPC proliferation and Shh-dependent cell branching. However, we failed to detect PDGF-Rα localization into the PC. Remarkably, ciliobrevin-mediated disruption of PC and reduction of OPC process extension was counteracted by recombinant Shh treatment, while PDGF had no effect. Therefore, while PDGF-Rα-dependent OPC proliferation and survival most probably does not initiate at the PC, still the integrity of this organelle and cilium-centered pathway is necessary for OPC survival and differentiation.
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spelling pubmed-45179002015-07-31 Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation Falcón-Urrutia, Paulina Carrasco, Carlos M. Lois, Pablo Palma, Veronica Roth, Alejandro D. PLoS One Research Article Primary Cilia (PC) are a very likely place for signal integration where multiple signaling pathways converge. Two major signaling pathways clearly shown to signal through the PC, Sonic Hedgehog (Shh) and PDGF-Rα, are particularly important for the proliferation and differentiation of oligodendrocytes, suggesting that their interaction occurs in or around this organelle. We identified PC in rat oligodendrocyte precursor cells (OPCs) and found that, while easily detectable in early OPCs, PC are lost as these cells progress to terminal differentiation. We confirmed the interaction between these pathways, as cyclopamine inhibition of Hedgehog function impairs both PDGF-mediated OPC proliferation and Shh-dependent cell branching. However, we failed to detect PDGF-Rα localization into the PC. Remarkably, ciliobrevin-mediated disruption of PC and reduction of OPC process extension was counteracted by recombinant Shh treatment, while PDGF had no effect. Therefore, while PDGF-Rα-dependent OPC proliferation and survival most probably does not initiate at the PC, still the integrity of this organelle and cilium-centered pathway is necessary for OPC survival and differentiation. Public Library of Science 2015-07-28 /pmc/articles/PMC4517900/ /pubmed/26218245 http://dx.doi.org/10.1371/journal.pone.0133567 Text en © 2015 Falcón-Urrutia et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Falcón-Urrutia, Paulina
Carrasco, Carlos M.
Lois, Pablo
Palma, Veronica
Roth, Alejandro D.
Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation
title Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation
title_full Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation
title_fullStr Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation
title_full_unstemmed Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation
title_short Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte Differentiation
title_sort shh signaling through the primary cilium modulates rat oligodendrocyte differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517900/
https://www.ncbi.nlm.nih.gov/pubmed/26218245
http://dx.doi.org/10.1371/journal.pone.0133567
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