TAp73 is a central transcriptional regulator of airway multiciliogenesis

Genes Dev. 2016 Jun 1;30(11):1300-12. doi: 10.1101/gad.279836.116. Epub 2016 Jun 2.


Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation.

Keywords: TAp73; TP73; airways; central transcriptional regulator; motile multiciliogenesis; p73.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Cilia / genetics*
  • Gene Expression Regulation / genetics*
  • Gene Knockout Techniques
  • Mice
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Respiratory Mucosa / cytology*
  • Respiratory Tract Infections / genetics
  • Respiratory Tract Infections / physiopathology


  • Nuclear Proteins
  • delta Np73, mouse