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p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network.


Marshall CBClayton B , Mays DJDeborah J , Beeler JSJ Scott , Rosenbluth JMJennifer M , Boyd KLKelli L , Santos Guasch GLGabriela L , Shaver TMTimothy M , Tang LJLucy J , Liu QQi , Shyr YYu , Venters BJBryan J , Magnuson MAMark A , Pietenpol JAJennifer A . Cell reports. 2016 3 15; 14(10). 2289-300


We report that p73 is expressed in multiciliated cells (MCCs), is required for MCC differentiation, and directly regulates transcriptional modulators of multiciliogenesis. Loss of ciliary biogenesis provides a unifying mechanism for many phenotypes observed in p73 knockout mice including hydrocephalus; hippocampal dysgenesis; sterility; and chronic inflammation/infection of lung, middle ear, and sinus. Through p73 and p63 ChIP-seq using murine tracheal cells, we identified over 100 putative p73 target genes that regulate MCC differentiation and homeostasis. We validated Foxj1, a transcriptional regulator of multiciliogenesis, and many other cilia-associated genes as direct target genes of p73 and p63. We show p73 and p63 are co-expressed in a subset of basal cells and suggest that p73 marks these cells for MCC differentiation. In summary, p73 is essential for MCC differentiation, functions as a critical regulator of a transcriptome required for MCC differentiation, and, like p63, has an essential role in development of tissues.