Ppargc1a Controls Ciliated Cell Development by Regulating Prostaglandin Biosynthesis
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved..
Cilia are microtubule-based organelles that function in a multitude of physiological contexts to perform chemosensing, mechanosensing, and fluid propulsion. The process of ciliogenesis is highly regulated, and disruptions result in disease states termed ciliopathies. Here, we report that peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (ppargc1a) is essential for ciliogenesis in nodal, mono-, and multiciliated cells (MCCs) and for discernment of renal tubule ciliated cell fate during embryogenesis. ppargc1a performs these functions by affecting prostaglandin signaling, whereby cilia formation and renal MCC fate are restored with prostaglandin E2 (PGE2) treatment in ppargc1a-deficient animals. Genetic disruption of ppargc1a specifically reduces expression of the prostanoid biosynthesis gene prostaglandin-endoperoxide synthase 1 (ptgs1), and suboptimal knockdown of both genes shows this synergistic effect. Furthermore, ptgs1 overexpression rescues ciliogenesis and renal MCCs in ppargc1a-deficient embryos. These findings position Ppargc1a as a key genetic regulator of prostaglandin signaling during ciliated cell ontogeny.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Cell reports - 33(2020), 6 vom: 10. Nov., Seite 108370 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chambers, Joseph M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.11.2021 Date Revised 12.11.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2020.108370 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317437410 |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Cilia are microtubule-based organelles that function in a multitude of physiological contexts to perform chemosensing, mechanosensing, and fluid propulsion. The process of ciliogenesis is highly regulated, and disruptions result in disease states termed ciliopathies. Here, we report that peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (ppargc1a) is essential for ciliogenesis in nodal, mono-, and multiciliated cells (MCCs) and for discernment of renal tubule ciliated cell fate during embryogenesis. ppargc1a performs these functions by affecting prostaglandin signaling, whereby cilia formation and renal MCC fate are restored with prostaglandin E2 (PGE2) treatment in ppargc1a-deficient animals. Genetic disruption of ppargc1a specifically reduces expression of the prostanoid biosynthesis gene prostaglandin-endoperoxide synthase 1 (ptgs1), and suboptimal knockdown of both genes shows this synergistic effect. Furthermore, ptgs1 overexpression rescues ciliogenesis and renal MCCs in ppargc1a-deficient embryos. These findings position Ppargc1a as a key genetic regulator of prostaglandin signaling during ciliated cell ontogeny | ||
| 650 | 4 | |a Journal Article | |
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