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  TAp73 is a central transcriptional regulator of airway multiciliogenesis.

Nemajerova, A., Kramer, D., Siller, S. S., Herr, C., Shomroni, O., Pena, T., et al. (2016). TAp73 is a central transcriptional regulator of airway multiciliogenesis. Genes and Development, 30(11), 1300-1312. doi:10.1101/gad.279836.116.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-F381-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-058D-0
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 Creators:
Nemajerova, A., Author
Kramer, D., Author
Siller, S. S., Author
Herr, C., Author
Shomroni, O., Author
Pena, T., Author
Suazo, C. G., Author
Glaser, K., Author
Wildung, M., Author
Steffen, H., Author
Sriraman, A., Author
Oberle, F., Author
Wienken, M., Author
Hennion, M., Author
Vidal, R., Author
Royen, B., Author
Alevra, M., Author
Schild, D., Author
Bals, R., Author
Dönitz, J., Author
Riedel, D.1, Author              Bonn, S., AuthorTakemaru, K. I., AuthorMoll, U. M., AuthorLize, M., Author more..
Affiliations:
1Facility for Electron Microscopy, MPI for biophysical chemistry, Max Planck Society, ou_578615              

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Free keywords: TAp73; p73; TP73; Motile multiciliogenesis; Central transcriptional regulator; Airways
 Abstract: 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.

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Language(s): eng - English
 Dates: 2016-06-022016-06-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1101/gad.279836.116
 Degree: -

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Title: Genes and Development
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 30 (11) Sequence Number: - Start / End Page: 1300 - 1312 Identifier: -