Shaggy regulates tissue growth through Hippo pathway in Drosophila  

作　　者：Honggang Wu Nannan Zhu Jiyong Liu Jun Ma Renjie Jiao 

机构地区：[1]Sino-French Hoffmann Institute,School of Basic Medical Sciences,Guangzhou Medical University Guangzhou 511436,China [2]State Key Laboratory of Respiratory Disease,Guangzhou Medical University,Guangzhou 511436,China [3]State Key Laboratory of Brain and Cognitive Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 10o10l,China [4]Women's Hospital and Institute of Genetics,Zhejiang University School of Medicine,Hangzhou 310058,China [5]Zhejiang Provincial Key Laboratory of Genetic&Developmental Disorders,Zhejang University School of Medicine,Hangzhou31l121,China

出　　处：《Science China(Life Sciences)》2022年第11期2131-2144,共14页中国科学（生命科学英文版）

基　　金：the National Key R&D Program of China(2021YFA0805800,2020YFA0803202,2018YFC1003203,2021YFC2700403);the National Natural Science Foundation of China(31970538,32000574,31871452);the Guangzhou Medical University Discipline Construction Funds(Basic Medicine)(JCXKJS2022A02);the 111 Project(D18010);the Local Innovative and Research Teams Project of Guangdong Perl River Talents Program(2017BT01S155);the Special Innovation Projects of Universities in Guangdong Province(2018KTSCX182);the Medical Scientific Research Foundation of Guangdong Province(A2019292);the Natural Science Foundation of Guangdong Province(2017A030310403)。

摘　　要：The evolutionarily conserved Hippo pathway coordinates cell proliferation,differentiation and apoptosis to regulate organ growth and tumorigenesis.Hippo signaling activity is tightly controlled by various upstream signals including growth factors and cell polarity,but the full extent to which the pathway is regulated during development remains to be resolved.Here,we report the identification of Shaggy,the homolog of mammalian Gsk3β,as a novel regulator of the Hippo pathway in Drosophila.Our results show that Shaggy promotes the expression of Hippo target genes in a manner that is dependent on its kinase activity.Loss of Shaggy leads to Yorkie inhibition and downregulation of Hippo pathway target genes.Mechanistically,Shaggy acts upstream of the Hippo pathway and negatively regulates the abundance of the FERM domain containing adaptor protein Expanded.Our results reveal that Shaggy is functionally required for Crumbs/Slmb-mediated downregulation of Expanded in vivo,providing a potential molecular link between cellular architecture and the Hippo signaling pathway.

关 键 词：DROSOPHILA growth control Hippo pathway Shaggy/Gsk3β Expanded 

分 类 号：Q343[生物学—遗传学]