SIGNALTRANSDUCTIONApoptosispropagatesthroughthecytoplasmastriggerwavesXianruiCheng1andJamesE.FerrellJr.1,2*Apoptosisisanevolutionarilyconservedformofprogrammedcelldeathcriticalfordevelopmentandtissuehomeostasisinanimals.Theapoptoticcontrolnetworkincludesseveralpositivefeedbackloopsthatmayallowapoptosistospreadthroughthecytoplasminself-regeneratingtriggerwaves.Wetestedthispossibilityincell-freeXenopuslaeviseggextractsandobservedapoptotictriggerwaveswithspeedsof~30micrometersperminute.Fractionationandinhibitorstudiesimplicatedmultiplefeedbackloopsingeneratingthewaves.Apoptoticoocytesandeggsexhibitedsurfacewaveswithspeedsof~30micrometersperminute,whichweretightlycorrelatedwithcaspaseactivation.Thus,apoptosisspreadsthroughtriggerwavesinbothextractsandintactcells.Ourfindingsshowhowapoptosiscanspreadoverlargedistanceswithinacellandemphasizethegeneralimportanceoftriggerwavesincellsignaling.Xenopuslaeviseggsarelargecells,~1.2mmindiameter,thatarenaturallyarrestedinmetaphaseofmeiosisII.Theeggsulti-matelyadoptoneoftwofates:Eithertheybecomefertilizedandentertheembryoniccellcycle,ortheyremainunfertilizedanddie,usuallythroughapoptosis.Apoptosisisarela-tivelynonperturbingformofcelldeathandmayallowthefrogtoresorboldoocytesandtocleanupanyeggsretainedinthebodywithoutprovokinganinflammatoryresponse(1).ThepowerfulbiochemicalapproachesprovidedbytheXenopussystemhavemadeXenopuseggsandextractsusefulmodelsystemsforthestudyofapoptosis(2,3).TheunusualsizeoftheXenopuseggraisesthequestionofhowanall-or-none,globalprocesssuchasapoptosisspreadsthroughthecell.Onepossibilityisthatapoptosisspreadsthroughtheeggbyrandomwalkdiffusion,ultimatelytakingoverallofthecytoplasm.Asecondpossibilityissuggestedbytheexistenceofmultiplepositiveanddouble-negativefeedbackloopsinthereg-ulatorynetworkthatcontrolsapoptosis(Fig.1A).Theseloopsmayallowapoptosistopropagatethroughself-regeneratingtriggerwaves.Triggerwavesarepropagatingfrontsofchemicalactivitythatmaintainaconstantspeedandamplitudeoverlargedistances.Theycana...
