Scribble Acts in the Drosophila Fat-Hippo Pathway to Regulate Warts Activity 英文参考文献.docVIP

ScribbleActsintheDrosophilaFat-HippoPathwayto RegulateWartsActivity ShilpiVerghese1,IndrayaniWaghmare1,HaileyKwon1,KatelinHanes1,MadhuriKango-Singh1,2,3* 1Department of Biology, University ofDayton, Dayton, Ohio, United States of America, 2Pre-Medical Programs, University of Dayton, Dayton, Ohio, United States of America,3CenterforTissueRegenerationandEngineeringatDayton,UniversityofDayton,Dayton,Ohio,UnitedStatesofAmerica Abstract Epithelial cells are the major cell-type for all organs in multicellular organisms. In order to achieve correct organ size, epithelial tissues need mechanisms that limit their proliferation, and protect tissues from damage caused by defective epithelial cells. Recently, the Hippo signaling pathway has emerged as a major mechanism that orchestrates epithelial development.HipposignalingisrequiredforcellstostopproliferationasintheabsenceofHipposignalingtissuescontinue toproliferateandproduceovergrownorgansortumors.StudiesinDrosophilahaveledthewayinprovidingaframework forhowHippoaltersthepatternofgenetranscriptionintargetcells,leadingtochangesincellproliferation,survival,and other behaviors. Scribble (Scrib) belongs to a class of neoplastic tumor suppressor genes that are required to establish apical-basalcellpolarity.Thedisruptionofapical-basalpolarityleadstouncontrolledcellproliferationofepithelialcells.The interactionofapicalbasalpolaritygeneswiththeHippopathwayhasbeenanareaofintenseinvestigation.Lossofscribhas beenknowntoaffectHippopathwaytargets,however,itsfunctionsintheHippopathwaystillremainlargelyunknown.We investigated the interactions of Scrib with the Hippo pathway. We present data suggesting that Drosophila scrib acts downstream of the Fat (Ft) receptor, and requires Hippo signaling for its growth regulatory functions. We show that Ft requiresScribtointeractwithExpanded(Ex)andDachs(D),andforregulatingWarts(Wts)levelsandstability,thusplacing ScribintheHippopathwaynetwork. Citation:VergheseS,WaghmareI,KwonH,HanesK,Kango-SinghM(20