TY - JOUR
T1 - Dual function of Yap in the regulation of lens progenitor cells and cellular polarity
AU - Song, Ji Yun
AU - Park, Raehee
AU - Kim, Jin Young
AU - Hughes, Lucinda
AU - Lu, Li
AU - Kim, Seonhee
AU - Johnson, Randy L.
AU - Cho, Seo Hee
N1 - Funding Information:
We thank Dr. Eric Olson for providing the Yap f/f strain. For mouse α-Pax6 antibody, the monoclonal antibody developed by Dr. Atsuhi Kawakami (Tokyo Institute of Technology, Japan) was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242, USA. This work was supported by the National Institute of Health Grant EY020578 (S.-H.C.) and RO1NS073112 (S.K.), and by a Research Grant from Shriners Hospitals for Children (S.-H.C. and S.K.).
PY - 2014/2/15
Y1 - 2014/2/15
N2 - 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.
AB - 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.
KW - Lens
KW - Organ size control
KW - Organogenesis
KW - Polarity
KW - Yap
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U2 - 10.1016/j.ydbio.2013.12.037
DO - 10.1016/j.ydbio.2013.12.037
M3 - Article
C2 - 24384391
AN - SCOPUS:84892897064
SN - 0012-1606
VL - 386
SP - 281
EP - 290
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -