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TAp73 is a master regulator of airway multiciliogenesis [RNA-Seq]

ABSTRACT: Comparative RNA seq analysis of WT and global p73KO Mouse Tracheal Epithelial Cell (MTECs) during the course of their differentiation (Air-Liquid Interface ALI D0, D4, D7, D14) aimed to determine the role of p73 in motile multiciliogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE75715 | GEO | 2016/05/05

SECONDARY ACCESSION(S): PRJNA305144

REPOSITORIES: GEO

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TAp73 is a master regulator of airway multiciliogenesis [sRNA-Seq]

Project description:Comparative small RNA seq analysis of WT and global p73KO Mouse Tracheal Epithelial Cell (MTECs) during the course of their differentiation (Air-Liquid Interface ALI D0, D4, D7, D14) aimed to determine the role of p73 in motile multiciliogenesis.

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TAp73 is a master regulator of airway multiciliogenesis

Project description:TAp73 is a master regulator of airway multiciliogenesis

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MiR-34b regulates multiciliogenesis during organ formation in zebrafish

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TAp73 is a central transcriptional regulator of airway multiciliogenesis.

Project description: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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