First Author | Marshall CB | Year | 2016 |
Journal | Cell Rep | Volume | 14 |
Issue | 10 | Pages | 2289-300 |
PubMed ID | 26947080 | Mgi Jnum | J:234561 |
Mgi Id | MGI:5790269 | Doi | 10.1016/j.celrep.2016.02.035 |
Citation | Marshall CB, et al. (2016) p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network. Cell Rep 14(10):2289-300 |
abstractText | 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. |