ta notes week 2 part 2

ta notes week 2 part 2 - BIPN144Week2Notes(part2)

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Unformatted text preview: BIPN144Week2Notes(part2) Note:ThishasnotbeenreviewedbyDr.Bierandmayhaveerrors.Always trusttheprofessoroverthesenotes. Dr.Bierstartedthelecturebyreviewingsomekeyterms,andmodifyingthe requirementsforclassificationasamorphogen Signalsactontheoutsideofcells(bybindingtoareceptor) TranscriptionFactorsactinsidethecells(bybindingtoDNAandeitheractivating orrepressingtranscription Morphogensmust: 1) Bepresentinagradedfashion 2) Elicitdistinctresponsesatdifferentconcentrations [Morphogensthataresignalsareusuallyproducedbyonesetofcellsandthen diffuseintoaregionthatisnotproducingthatsignal.This(alongwiththesink) establishesthegradient] Dorsal,howeverisaweirdTFmorphogen. Dr.BierthenreviewedtheeffectsofDorsalinthedevelopingflyembryo [figure37a] Herethetoplayer(yellow)isectoderm,andwillproduceskin. Themiddlelevel(blue)isneuralectoderm,andwillproduceneuronsandventral skin. Thebottomlevel(red)ismesoderm,andwillproducefatbloodandmuscle. Theendodermisnotshowninthisimage. DrBierthenspentsometimegoingoverdifferentmutantscenarios. Considerthemesodermlayer.Iftwistorsnailwereknockedout,whatwould happen? NoTwist=nomesoderm(mesodermgeneswouldnotbeactivated) NoSnail=superficiallythesame,nomesoderm.HOWEVER,thisoccursfora differentreason.Mesodermgeneswillbeactivatedbytwist,butnothingwill represstheexpressionofneuralgenes.Thismeansthatthecellswillbetryingto becomeBOTHMesodermANDNeuraltissue.Thisseverelyconfusesthecells,and theyselfdestruct.(ASC+Twist=CellDeath) NowconsidertheNeuroectodermlayer NoASC=Noneurons NoBrk=Crazyskinoverexpression,asDPPwillnotbeproperlyinhibitedinthe neuroectoderm,resultingintoomuchectoderm. NoSog=SimilartoNoBrk.DPPwillnotbeproperlyblockedintheneuroectoderm resultingincrazyskinoverexpresion. Dorsaldoesn'tlastverylong,sotheembryoneedstokeepdevelopmentgoingonits own.DPPisfuelsbyapowerfulpositivefeedbackloop.("DPPislikeabulldozer") PerhapsbecauseDPPissopowerful,therearetwopathwaysdevotedtoblockingit (SogandBrk) SowhatwouldthedifferencebebetweenaDPPKOandaDPP/SogDoubleKO? Probablynotverymuch.SogrepressesDPP.IfthereisnoDPP,thenthereisnoneed torepressit,makingSogvirtuallyuseless. Dr.BierthenspentsometimetalkingaboutRhomboid(Rho).Rhoisresponsiblefor makingventralskin.Thisisnotthatimportant,however.Whatisimportantisthat RhoisagoodmodeltoexplainhowactivatorandrepressorTF'swork. HowdoestheembryoactivateRhoinonlytheneuroectodermregion? TranscriptionFactorsbindtoDNAwithdifferentaffinities.Dr.Bierdescribedthisby comparingHighaffinitybindingtoreallystrong,thick,denseVelcro. lowaffinitybindingattaches,releasesandreattachesfrequently,likeweakpoor qualityVelcro. Dorsal(whichactivatessnail)bindstotheSnailgenewithLowaffinity(weak Velcro).ThisisokaybecausewhereSnailissupposedtobeactive(mesoderm), thereisalotofDorsal.Intheneuroectoderm,thereisnotenoughDorsaltoactivate Snail. DorsalbindstotheRhogenewithHighaffinity,andactivatesit.Thisisgoodbecause whereRhoisactive(Neuroectoderm),thereisn'tmuchdorsal. TheSnailgeneproducestheSnailTF.TheSnailTFbindstoandrepressestheRho gene.SowherethereisenoughDorsaltoactivateSnail,SnailwillrepressRho.If thereisnotenoughDorsaltoactivateSnail(lowaffinityweakvelcro),butenough toActivateRho(highaffinitystrongvelcro),thenRhowillbeexpressed.Ifthereis noDorsal,NeitherSnailnorRhowillbeexpressed. SeeFigure38 AndNowontoourFirstVertibrateSystem,theXenopusEmbryo! SeeFigure5.1(GogogadgetFrog!) IntrinsicFacorspatternegg(maternalfactors).Example:dorsal. Extrinsicfactorsthingsthatworkfrooutsidetheegg.Example:gravityinsome eggs,orthepointofspermentry(frog)duringfertiliation. Thefrogeggispigmented,anddividedinto2hemispheres,theanimalandthe vegetalhemispheres.Theanimalhemispherewillgiverisetotheectodermand mesoderm.Thevegetalhemispheregivesrisetocarrotsandcabbagesandthelike. Justkidding,itgivesrisetotheendoderm.Thereare"profoundmolecular differences(intrinsicfactors)localizedtothedifferenthemispheres." Thespermcanentertheegganywhereinanarrowstripjustontheanimalsideof theanimal/vegetalequator.Thepointofspermentrybecomestheventralpole.The oppositesidebecomesthedorsalpole. Priortofertilizationtherearelatent(asopposedtoactive)dorsalizingfactorsatthe vegetalpole.Justbeneaththeeggmembraneisthecortexmaterial.Whenthesperm enterstheegg,thecortex"violentlybeats"itawayfromthepointofspermentry. Thisiscalledcorticalrotation,orasDr.BierputitSwishing."Thiscorticalrotation movesthedorsalizingfactorsfromthevegetalpoletothedorsalpole,andthey becomeactive. ThevegetalhemisphereproducesaTFcalledVegT.VegTisanexampleofwhatDr, Biercallsthe"forexportonly"signalingconcept.Thisiswhencellsmakeasignal theycantrespondto,soonlytheneighboringcellsrespondtoit.Thissystemisvery usefulfordrawingalinebetweentwodomains. VegThas2effects: 1) (+)Itactivatesmesoderminducingsignals 2) ()Itrepressesresponsetomesoderminducers(atleastintheVegetal Hemisphere) ThusVegTactivatesMesoderminducingsignalsintheregionnexttothe Animal/Vegetalequator. NowtheactivedorsalizingfactorsgetgoingandsecreteaTFcalledBCatenin. ...
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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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