title: Dual function of Yap in the regulation of lens progenitor cells and cellular polarity.
abstract: Hippo-Yap signaling has been implicated in organ size determination via its regulation of cell proliferation, growth and apoptosis (Pan, 2007). The vertebrate lens comprises only two major cell types, lens progenitors and differentiated fiber cells, thereby providing a relatively simple system for studying size-controlling mechanisms. In order to investigate the role of Hippo-Yap signaling in lens size regulation, we conditionally ablated Yap in the developing mouse lens. Lens progenitor-specific deletion of Yap led to near obliteration of the lens primarily due to hypocellularity in the lens epithelium (LE) and accompanying lens fiber (LF) defects. A significantly reduced LE progenitor pool resulted mainly from failed self-renewal and increased apoptosis. Additionally, Yap-deficient lens progenitor cells precociously exited the cell cycle and expressed the LF marker, β-Crystallin. The mutant progenitor cells also exhibited multiple cellular and subcellular alterations including cell and nuclear shape change, organellar polarity disruption, and disorganized apical polarity complex and junction proteins such as Crumbs, Pals1, Par3 and ZO-1. Yap-deficient LF cells failed to anchor to the overlying LE layer, impairing their normal elongation and packaging. Furthermore, our localization study results suggest that, in the developing LE, Yap participates in the cell context-dependent transition from the proliferative to differentiation-competent state by integrating cell density information. Taken together, our results shed new light on Yap's indispensable and novel organizing role in mammalian organ size control by coordinating multiple events including cell proliferation, differentiation, and polarity.
authors.affiliation: Shriners Hospitals Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Song
authors.affiliation: Shriners Hospitals Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Raehee
authors.initials: R
authors.lastname: Park
authors.affiliation: Shriners Hospitals Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Shriners Hospitals Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Lucinda
authors.initials: L
authors.lastname: Hughes
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.affiliation: Shriners Hospitals Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Seonhee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Johnson
authors.affiliation: Shriners Hospitals Pediatric Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, United States. Electronic address: seo.hee.cho@temple.edu.
authors.forename: Seo-Hee
authors.initials: SH
authors.lastname: Cho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D016764:Cell Polarity / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D000090683:Hippo Signaling Pathway; D017403:In Situ Hybridization; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology*; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*; D000091102:YAP-Signaling Proteins; D038204:beta-Crystallins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D017931:DNA Primers; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D038204:beta-Crystallins; D017346:Protein Serine-Threonine Kinases
keywords: Lens; Organ size control; Organogenesis; Polarity; Yap