Ppargc1a Controls Ciliated Cell Development by Regulating Prostaglandin Biosynthesis
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...
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Veröffentlicht in: | Cell reports (Cambridge) 2020-11, Vol.33 (6), p.108370-108370, Article 108370 |
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Zusammenfassung: | 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.
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•ppargc1a is required for ciliogenesis in nodal, mono-, and multiciliated cells•ppargc1a mitigates renal tubule ciliated cell fate discernment during embryogenesis•Ppargc1a controls PGE2 production through the prostanoid biosynthesis gene ptgs1
Prostaglandin signaling has key roles in ciliated cell fate decisions during nephron development as well as the process of ciliogenesis. Chambers et al. show that activity of Ppargc1a regulates ciliogenesis in zebrafish embryos by controlling production of the prostaglandin PGE2 via the prostaglandin pathway component Ptgs1. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2020.108370 |