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Crumbs proteins stabilize the cone mosaics of photoreceptors and improve vision in zebrafish
Authors:Qinlong Hao  Mingjie Zheng  Kechao Weng  Yumei Hao  Yao Zhou  Yuchen Lin  Feng Gao  Ziqi Kou  Shoji Kawamura  Ke Yao  Pinglong Xu  Jinghai Chen  Jian Zou
Affiliation:1. Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;2. The Institute of Translational Medicine, Zhejiang University, Hangzhou 310058, China;3. Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;4. Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan;5. Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310058, China;6. MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China;1. State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China;2. Key Laboratory of Development and Application of Rural Renewable Energy (Ministry of Agriculture), Biomass Energy Technology Research Centre, Biogas Institute of Ministry of Agriculture, Chengdu, Sichuan 610041, China;1. Department of Rehabilitation Medicine, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China;2. Center for Plant Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China;3. Tsinghua-Peking Center for Life Sciences, Beijing 100084, China;4. National Institute of Biological Sciences, Zhongguancun Life Science Park, Beijing 102206, China;1. Hunan Provincial Key Laboratory of Phytohormones and Growth Development, College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha 410128, China;2. Department of Botany, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;3. Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;1. State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, China;2. National Centre for Plant Gene Research (Beijing), Innovation Academy for Seed Design, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;3. College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing 100039, China
Abstract:Although the unique organization of vertebrate cone mosaics was first described long ago,both their underlying molecular basis and physiological significance are largely unknown.Here,we demonstrate that Crumbs proteins,the key regulators of epithelial apical polarity,establish the planar cellular polarity of photoreceptors in zebrafish.Via heterophilic Crb2a-Crb2b interactions,the apicobasal polarity protein Crb2b restricts the asymmetric planar distribution of Crb2a in photoreceptors.The planar polarized Crumbs proteins thus balance intercellular adhesions and tension between photoreceptors,thereby stabilizing the geometric organization of cone mosaics.Notably,loss of Crb2b in zebrafish induces a nearsightedness-like phenotype in zebrafish accompanied by an elongated eye axis and impairs zebrafish visual perception for predation.These data reveal a detailed mechanism for cone mosaic homeostasis via previously undiscovered apical-planar polarity coordination and propose a pathogenic mechanism for nearsightedness.
Keywords:Crumbs proteins  Apical polarity  Planar cellular polarity  Cone mosaics  Nearsightedness  Visual perception
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