Prostaglandin signaling regulates renal multiciliated cell specification and maturation

Research output: Contribution to journalArticle

  • External authors:
  • Amanda N. Marra
  • Basma D. Adeeb
  • Brooke E. Chambers
  • Bridgette E. Drummond
  • Marisa Ulrich
  • Amanda Addiego
  • Meghan Springer
  • Shahram J. Poureetezadi
  • Joseph M. Chambers
  • Rebecca A. Wingert

Abstract

Multiciliated cells (MCCs) are specialized epithelia with apical bundles of motile cilia that direct fluid flow. MCC dysfunction is associated with human diseases of the respiratory, reproductive, and central nervous systems. Further, the appearance of renal MCCs has been cataloged in several kidney conditions, where their function is unknown. Despite their pivotal health importance, many aspects of MCC development remain poorly understood. Here, we utilized a chemical screen to identify molecules that affect MCC ontogeny in the zebrafish embryo kidney, and found prostaglandin signaling is essential both for renal MCC progenitor formation and terminal differentiation. Moreover, we show that prostaglandin activity is required downstream of the transcription factor ets variant 5a (etv5a) during MCC fate choice, where modulating prostaglandin E 2 (PGE 2 ) levels rescued MCC number. The discovery that prostaglandin signaling mediates renal MCC development has broad implications for other tissues, and could provide insight into a multitude of pathological states.

Bibliographical metadata

Original languageEnglish
Pages (from-to)8409-8418
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number17
Early online date4 Apr 2019
DOIs
Publication statusPublished - 23 Apr 2019