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Ppargc1a Regulates Prostaglandin Signaling to Control Ciliogenesis and Renal Multiciliated Cell Fate Choice During Development
Author(s) -
Chambers Joseph M.,
Addiego Amanda,
Wingert Rebecca A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05356
Subject(s) - ciliogenesis , cilium , biology , microbiology and biotechnology
Cilia are microtubule‐based organelles that function in a multitude of physiological contexts to perform chemosensing, mechanosensing, or fluid propulsion. The process of ciliogenesis is highly regulated and disruptions result in disease states termed ciliopathies. The genetic and molecular events that lead to dysfunctional ciliated cells are still not fully understood. Here, we show novel roles for peroxisome proliferator‐activated receptor gamma 1 alpha ( ppargc1a ) during ciliogenesis in mono‐ and multiciliated cells (MCCs) as well as discernment of renal tubule MCC fate choice during embryogenesis. We discovered that ppargc1a performs both roles by affecting prostaglandin levels, where cilia formation and renal MCC fate were restored with prostaglandin E 2 (PGE 2 ) treatment. Genetic disruption of ppargc1a specifically reduced expression of the prostanoid biosynthesis gene prostaglandin‐endoperoxide synthase 1 ( ptgs1 ), and suboptimal knockdown of both genes revealed a synergistic effect. Further, ptgs1 overexpression rescued ciliogenesis and renal MCCs in ppargc1a deficient embryos. These findings position Ppargc1a as an essential genetic regulator of prostaglandin synthesis during ciliated cell ontogeny. Support or Funding Information National Institutes of Health (R01DK100237 to R.A.W.), a 2019 University of Notre Dame Advanced Diagnostics and Therapeutics Graduate Fellowship Award (to J.M.C.), and a 2019 University of Notre Dame College of Science Summer Undergraduate Research Fellowship Award (to A.A.)