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Abstract: SA-PO545

Genetic Mechanisms of Multiciliated Cell Development during Renal Ontogeny

Session Information

  • Developmental Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Developmental Biology and Inherited Kidney Diseases

  • 401 Developmental Biology


  • Marra, Amanda N., University of Notre Dame, Notre Dame, Indiana, United States
  • Wingert, Rebecca A., University of Notre Dame, Notre Dame, Indiana, United States

Multiciliated cells (MCCs) are found in a wide variety of species and tissues, ranging from the embryonic kidney of frogs and fish to the reproductive and respiratory systems of mammals. Differentiation of MCCs has become an increasingly attractive area of research due to their association with fluid flow and disease. There is evidence for a core, conserved pathway of MCC development that includes the Notch signaling pathway as a negative regulator of MCC fate.


The embryonic zebrafish kidney, or pronephros, has emerged as a useful tool to study MCC genesis in vivo, where the transcription factor mecom acts upstream of Notch to restrict MCC development while Retinoic Acid (RA) signaling promotes MCC fate by inhibiting mecom and promoting expression of the ETS transcription factor etv5a.


Here, we report phenotype analysis of the etv5asa16031 allele, which encodes a nonsense mutation in the conserved ETS DNA-binding domain of etv5a. Embryos with one copy of this allele display decreased expression of MCCs, suggesting that etv5a is a haploinsufficient gene. Next, we found that mecom inhibits etv5a expression in the kidney, as knockdown of mecom caused an expansion of the etv5a domain. Additionally, we have identified a role for the transcription factor irx2a in MCC development, where knockdown of irx2a results in a loss of MCCs similar to that seen in etv5a-deficient embryos. Lastly, we have uncovered a role for prostaglandin (Pg) signaling in MCC development through a large-scale chemical screen. Inhibition of the Pg pathway via Indomethacin or concomitant knockdown of the Pg biosynthesis enzymes Cox1 and 2 significantly reduced MCC number. Interestingly, Pg inhibition did not produce a detectable change in the etv5a pronephros domain, suggesting that Pg signaling promotes MCC development separate from etv5a.


In conclusion, we have discovered a novel relationship between etv5a and mecom during MCC development, established irx2a as a MCC fate factor, and have identified an essential role for Pg signaling in MCC genesis.


  • NIDDK Support