title: The hippo pathway effector Yap controls patterning and differentiation of airway epithelial progenitors.
abstract: How epithelial progenitor cells integrate local signals to balance expansion with differentiation during organogenesis is still little understood. Here, we provide evidence that the Hippo pathway effector Yap is a key regulator of this process in the developing lung. We show that when epithelial tubules are forming and branching, a nucleocytoplasmic shift in Yap localization marks the boundary between the airway and the distal lung compartments. At this transition zone, Yap specifies a transcriptional program that controls Sox2 expression and ultimately generates the airway epithelium. Without Yap, epithelial progenitors are unable to properly respond to local TGF-β-induced cues and control levels and distribution of Sox2 to form airways. Yap levels and subcellular localization also markedly influence Sox2 expression and differentiation of adult airway progenitors. Our data reveal a role for the Hippo-Yap pathway in integrating growth-factor-induced cues in the developing and adult lung potentially key for homeostasis and regeneration repair.
authors.affiliation: Columbia Center for Human Development, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Mahoney
authors.affiliation: Columbia Center for Human Development, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Munemasa
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Aleksander D
authors.initials: AD
authors.lastname: Szymaniak
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Xaralabos
authors.initials: X
authors.lastname: Varelas
authors.affiliation: Columbia Center for Human Development, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: wvc2104@columbia.edu.
authors.forename: Wellington V
authors.initials: WV
authors.lastname: Cardoso
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019521:Body Patterning; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D000090683:Hippo Signaling Pathway; D008168:Lung / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D016212:Transforming Growth Factor beta; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D017346:Protein Serine-Threonine Kinases