Dual function of Yap in the regulation of lens progenitor cells and cellular polarity.
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.
['Song|Ji Yun|JY|', 'Park|Raehee|R|', 'Kim|Jin Young|JY|', 'Hughes|Lucinda|L|', 'Lu|Li|L|', 'Kim|Seonhee|S|', 'Johnson|Randy L|RL|', 'Cho|Seo-Hee|SH|']
D048868:Adaptor Proteins, Signal Transducing D000818:Animals D018797:Cell Cycle Proteins D016764:Cell Polarity D048430:Cell Shape D017931:DNA Primers D004847:Epithelial Cells D005455:Fluorescent Antibody Technique D018507:Gene Expression Regulation, Developmental D000090683:Hippo Signaling Pathway D017403:In Situ Hybridization D007908:Lens, Crystalline D051379:Mice D010750:Phosphoproteins D017346:Protein Serine-Threonine Kinases D015398:Signal Transduction D013234:Stem Cells D000091102:YAP-Signaling Proteins D038204:beta-Crystallins
Yap Lens Polarity Organ size control Organogenesis