BIPN 144 Week 3 Notes (part1)

BIPN 144 Week 3 Notes (part1) - BIPN144Week3Notes(part1)

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Unformatted text preview: BIPN144Week3Notes(part1) Note:ThishasnotbeenreviewedbyDr.Bierandmayhaveerrors.Always trusttheprofessoroverthesenotes. Dr.BierStartedofthelecturebyreviewingwhathehadpreviouslytaughtaboutthe xenopus(frog)embryo Firsthegavethefollowingexamplesofintrinsicandextrinsicfactors: Intrinsicdorsal(fly),animalvegetaldistinction(frog),VegT(frog) Extrinsicpointofspermentry(frog) Hethenreviewedtheactivefactorsinanewlyfertilizedfrogembryo. Briefly,whereverthespermenterstheegg(whichwillbenearthe`equator'inthe animalhemisphere)becomestheventralpole.Fertilizationbeginsthe"swishing" knownascorticalrotation,whichmovesthelatentdorsalizingfactorsfromthe vegetalpoletothedorsalpoleandactivatesthem.Thedorsalpoleisoppositethe ventralpole(whichisthepointofspermentry).Thenowactivedorsalizingfactors beginproducingBcatenin(whichisaTF). Atthesametimethatthisistakingplace,anotherfactorcalledVegT(aTF)isspread throughoutthevegetalhemisphere,andbeginstakingpartin"exportonly signaling."Exportonlysignalinghastwocharacteristics: 1) itactivatesexpressionsignalsand 2) itrepressestheresponsetothosesignals. Exportonlysignalingisveryusefulfordrawingalinebetweentwodomains.VegT activatestheexpressionofmesoderminducingsignals,andrepressestheresponse tothosemesodermexpressingsignals.Hiscausesathinstripofmesodermtoform ontheanimalsideoftheanimal/vegetaldivision. Bcateninsignalingfromthedorsalpoledividesthemesoderminto3regions.The dorsalmostregionbecomestheSpemannorganizer,whichwillformthenotochord. Thenextregiondownbecomesmuscleandheart.Theventralmostregionforms blood. Thedorsalmostportionoftheanimalhemispherewillbecometheneuroectoderm. Theremainderwillbecomeskin.(exceptofcourseforthemesoderm). DrBierthenperformedhisgruesomedemonstrationofgastrulationusinghissock. Thisisveryhardtoexplainwithoutanadditionalimage,butessentially,thevegetal hemispherebeginstofoldinonitself,whichisfollowedbythemesoderm,making whatwaspreviouslyanteriormesodermintoposteriormesoderm.Veryconfusing,I willgooverthisinsection. Dr.Bierthenswitchedgearsandwentbacktoouroldfriendthefruitfly,Figure 3.7A HethenspentsomeconsiderabletimeonDPPsignaling.Hepointedoutthatmore DPPisrequiredtocarryoutthepositivefunctionsofDPP(activatingskingenes) thanisrequiredtocarryoutthenegativefunctionsofDPP(inhibitingneural induction). TheDPPsignalisverystrong(likeabulldozer).ItissostrongthatBOTHBrinker andSogarerequiredtokeepitfromoverrunningtheneuroectoderm. BrinkershutsoffresponsestoDPP SogbindstoDPP,preventingitfrombindingtoitsownreceptorandactivating itself. Dr.Bierthentooksometimetoconsiderpossiblemutants.(Andinsinuatedthat understandinghowmutantsworkwillbevaluablefortheexam).Hementioned: ADPPknockoutmutantthiswouldturnonneuralinductioninthedorsalmost region,andtheabsenceofskin. SogorBrkknockoutmutant"bluepartwouldbecomeyellow"theectoderm regionwouldovertaketheneuroectoderm,andeventuallywouldtakeoverthe mesodermaswell. DPP/SogdoublemutantsameasaDPPmutant."Ifthewolfisdeaddoyoureally needagun?" DrBierthenputupthisimageoftheDPPpathway: ThisFiguredemonstrateshowDPPsignalingworks,andhowitcanbeinhibitedby Sog.TheDPPproteinisasignal,whichissecretedandbindstotheDPPreceptor. ActivationoftheDPPreceptorcausestheactivationofnonneuralgenesand repressesneuralgenes.SogbindstheDPPproteinandpreventsitfrombindingits receptor.(BrinkeractsinthenucleusasaTFtostopDPP). DrBierthenputupFigure310: Hethenhighlightedthefollowingpoints: ASCgenesmustbeturnedoffifneuralfateisnotdesired DPPrepressesASC SogandBrkblockDPP Sogisactivatedbydorsal IttakesBOTHBrkandSogtostopDPP Remember,Dorsalisnotapermanentsignal,itstartsthingsgoing,butdoesn'tlast verylong. DrBierthenmovedbacktothedevelopingFrogembryoandstarteddiscussingthe experimentsofDrSpemannandhisassistantwho'snameIcantspell. TheydemonstratedthattransplantingtheSpemannorganizerregionoftheembryo intoanewrecipientembryoresultedintwoheadedfrogs.Thisleadtotheideathat theSpemannorganizerwascapableofredirectingepidermalcellstobecome notochordbysecreting"neuralinducers."Thisledtoaseriesof`animalcap'studies wheretheanteriorsliceoftheanimalcapwasremoved.Thisanimalcapwasthen showntobecomeepidermaltissueifleftalone,orneuraltissueifplacedonasliceof dorsalmesoderm.Thisstrengthenedthebeliefintheexistenceofneuralizing factorsandthenotionthatinvertebrates,epidermiswasthedefaultandneural tissuehadtobeinduced.ThisprobablyincorrectconceptsurvivedatleastuntilDr. Bierwasingradschool.However,aratherimpressiveexperimentchangedtheway peoplethoughtaboutthings. Thisexperimentdemonstratesthatintheabsenceofanysignal,ectodermcells becomeneuraltissue.BMP4(thevertebrateequivalentofDPP)isrequiredto produceskin.AndChordin(thevertebrateequivalentofSog)caninhibitBMP4, maintainingtheneuralfate. ...
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This note was uploaded on 11/10/2010 for the course BIPN BIPN 144 taught by Professor Bier during the Spring '10 term at UCSD.

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