Seminar - Ute Moll

photo of Dr. Ute Moll
November 20, 2017 - 12:00pm
Location: 
601 Fairchild

Department of Pathology

School of Medicine

Stony Brook University

Host: Carol Prives

Title: TAp73 is a master transcriptional regulator of airway multiciliogenesis upstream of FoxJ1

Abstract: Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease. They are
essential for cleaning airways from inhaled pollutants and pathogens. However, despite their clear
significance for human disease, the transcriptional control that governs MCC multiciliogenesis
remains poorly understood. Surprisingly, we now identify TP73, a p53 homolog, to govern the
program for airway multiciliogenesis. We show that 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 in the later differentiation stages of MCC progenitors.
Mechanistically, cross-species genomic analyses and complete cilial rescue of knockout MCCs
identify TAp73 as the conserved master transcriptional integrator of multiciliogenesis. TAp73 acts
upstream of known central nodes by directly activating key regulators FoxJ1, Rfx2, Rfx3, miR34bc,
plus nearly 50 structural and functional ciliary genes, some of which are associated with human
ciliopathies. Our results provide deep mechanistic insights into TAp73’s central role in ciliogenesis.

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