Download Your Inner Fish - 06_Chapter Six

CHAPTERSIX
THEBEST-LAID(BODY)PLANS
Weareapackageofabouttwotrillioncellsassembledina
verypreciseway.Ourbodiesexistinthreedimensions,
withourcellsandorgansintheirproperplaces.Theheadis
ontop.Thespinalcordistowardourback.Ourgutsareon
thebellyside.Ourarmsandlegsaretothesides.Thisbasic
architecturedistinguishesusfromprimitivecreatures
organizedasclumpsordisksofcells.
Thesamedesignisalsoanimportantpartofthebodies
ofothercreatures.Likeus,fish,lizards,andcowshave
bodiesthataresymmetricalwithafront/back,top/bottom,
andleft/right.Theirfrontends(correspondingtothetopof
anuprighthuman)allhaveheads,withsenseorgansand
brainsinside.Theyhaveaspinalcordthatrunsthelength
ofthebodyalongtheback.Alsolikeus,theyhaveananus,
whichisattheoppositeendoftheirbodiesfromthemouth.
Theheadisontheforwardend,inthedirectionthey
typicallyswimorwalk.Asyoucanimagine,“anus-forward”
wouldn’tworkverywellinmostsettings,particularly
aquaticones.Socialsituationswouldbeaproblem,too.
129
Itismoredifficulttofindourbasicdesigninreally
primitiveanimals—jellyfish,forexample.Jellyfishhavea
differentkindofbodyplan:theircellsareorganizedinto
disksthathaveatopandbottom.Lackingafrontandback,
aheadandtail,andaleftandright,jellyfishbody
organizationappearsverydifferentfromourown.Don’t
evenbothertryingtocompareyourbodyplanwitha
sponge.Youcouldtry,butthemerefactthatyouwere
tryingwouldrevealsomethingmorepsychiatricthan
anatomical.
Toproperlycompareourselveswiththeseprimitive
animals,weneedsometools.Justaswithheadsandlimbs,
ourhistoryiswrittenwithinourdevelopmentfromeggto
adult.Embryosholdthecluestosomeoftheprofound
mysteriesoflife.Theyalsohavetheabilitytoderailmy
plans.
THECOMMONPLAN:COMPARINGEMBRYOS
Ienteredgraduateschooltostudyfossilmammalsand
endedupthreeyearslaterstudyingfishandamphibiansfor
mydissertation.Myfallfromgrace,ifyouwanttocallit
that,happenedwhenIstartedtolookatembryos.Wehada
lotofembryosinthelab:salamanderlarvae,fishembryos,
evenfertilizedchickeneggs.I’droutinelypopthemunder
themicroscopetoseewhatwasgoingon.Theembryosof
allthespecieslookedlikelittlewhitishbatchesofcells,no
130
morethananeighthofaninchlong.Itwasexciting
watchingdevelopmentprogress;astheembryogotbigger,
theyolk,itsfoodsupply,gotsmallerandsmaller.Bythe
timetheyolkwasgone,theembryowasusuallybigenough
tohatch.
Watchingtheprocessofdevelopmentbroughtabouta
hugeintellectualtransformationinme.Fromsuchsimple
embryonicbeginnings—smallblobsofcells—came
wonderfullycomplexbirds,frogs,andtroutcomprising
trillionsofcellsarrangedinjusttherightway.Butthere
wasmore.Thefish,amphibian,andchickenembryoswere
likenothingIhadeverseenbeforeinbiology.Theyall
lookedgenerallyalike.Allofthemhadaheadwithgill
arches.Allofthemhadalittlebrainthatbeganits
developmentwiththreeswellings.Allofthemhadlittle
limbbuds.Infact,thelimbsweretobecomemythesis,the
focusofmynextthreeyears’work.Here,incomparinghow
theskeletondevelopedinbirds,salamanders,frogs,and
turtles,Iwasfindingthatlimbsasdifferentasbirdwings
andfroglegslookedverysimilarduringtheirdevelopment.
Inseeingtheseembryos,Iwasseeingacommon
architecture.Thespeciesendeduplookingdifferent,but
theystartedfromagenerallysimilarplace.Lookingat
embryos,italmostseemsthatthedifferencesamong
mammals,birds,amphibians,andfishsimplypalein
comparisonwiththeirfundamentalsimilarities.ThenI
learnedoftheworkofKarlErnstvonBaer.
Inthe1800s,somenaturalphilosopherslookedto
131
embryostotrytofindthecommonplanforlifeonearth.
ParamountamongtheseobserverswasKarlErnstvon
Baer.Borntoanoblefamily,heinitiallytrainedtobea
physician.Hisacademicmentorsuggestedthathestudy
chickendevelopmentandtrytounderstandhowchicken
organsdeveloped.
Unfortunately,vonBaercouldnotaffordincubatorsto
workonchickens,norcouldheaffordmanyeggs.Thiswas
notverypromising.Luckyforhim,hehadanaffluentfriend,
ChristianPander,whocouldaffordtodotheexperiments.
Astheylookedatembryos,theyfoundsomething
fundamental:allorgansinthechickencanbetracedtooneof
threelayersoftissueinthedevelopingembryo.Thesethree
layersbecameknownasthegermlayers.Theyachieved
almostlegendarystatus,whichtheyretaineventothisday.
Pander’sthreelayersgavevonBaerthemeanstoask
importantquestions.Doallanimalssharethispattern?Are
thehearts,lungs,andmusclesofallanimalsderivedfrom
theselayers?And,importantly,dothesamelayersdevelop
intothesameorgansindifferentspecies?
VonBaercomparedthethreelayersofPander’schicken
embryoswitheverythingelsehecouldgethishandson:
fish,reptiles,andmammals.Yes,everyanimalorgan
originatedinoneofthesethreelayers.Significantly,the
threelayersformedthesamestructuresineveryspecies.
Everyheartofeveryspeciesformedfromthesamelayer.
Anotherlayergaverisetoeverybrainofeveryanimal.And
soon.Nomatterhowdifferentthespecieslookasadults,as
132
tinyembryostheyallgothroughthesamestagesof
development.
Tofullyappreciatetheimportanceofthis,weneedto
lookagainatourfirstthreeweeksafterconception.Atthe
momentoffertilization,majorchangeshappeninsidethe
egg—thegeneticmaterialofthespermandeggfusesand
theeggbeginstodivide.Ultimately,thecellsformaball.In
humans,overaboutfivedays,thesingle-cellbodydivides
fourtimes,toproduceaballofsixteencells.Thisballof
cells,knownasablastocyst,resemblesafluid-filledballoon.
Athinsphericalwallofcellssurroundssomefluidinthe
center.Atthis“blastocyststage”therestilldoesnotappear
tobeanybodyplan—thereisnofrontandback,and
certainlytherearenotyetanydifferentorgansortissues.
Onaboutthesixthdayafterconception,theballofcells
attachestoitsmother’suterusandbeginstheprocessof
connectingtoitsothatmotherandembryocanjoin
bloodstreams.Thereisstillnoevidenceofthebodyplan.It
isafarcryfromthisballofcellstoanythingthatyou’d
recognizeasanymammal,reptile,orfish,muchlessa
human.
Ifwearelucky,ourballofcellshasimplantedinour
mother’suterus.Whenablastocystimplantsinthewrong
place—whenthereisan“ectopicimplantation”—the
resultscanbedangerous.About96percentofectopic
implantationshappenintheuterine(orfallopian)tubes,
nearwhereconceptionhappens.Sometimesmucusblocks
theeasypassageoftheblastocysttotheuterus,causingit
133
toimplantimproperlyinthetubes.Ectopicpregnancycan
causevarioustissuerupturesifnotcaughtintime.Inreally
rarecases,theblastocystisexpelledintothemother’sbody
cavity,thespacebetweenhergutsandbodywall.Ineven
rarercases,theseblastocystswillimplantontheoutside
liningofthemother’srectumoruterusandthefetus
developstofullterm!Althoughthesefetusescan
sometimesbedeliveredbyanabdominalincision,such
implantationisgenerallyverydangerousbecauseit
increasestheriskofmaternaldeathbybleedingbyafactor
of90,ascomparedwithanormalimplantationinsidethe
uterus.
Inanyevent,atthisstageofdevelopmentweare
extremelyhumble-lookingcreatures.Aroundthebeginning
ofoursecondweekafterconception,theblastocysthas
implanted,withonepartoftheballembeddedinthewallof
theuterus,andtheotherfree.Thinkofaballoonpushed
intoawall:thisflatteneddiskbecomesthehumanembryo.
Ourentirebodyformsfromonlythetoppartofthisball,the
partthatismushedintothewall.Thepartoftheblastocyst
belowthediskcoverstheyolk.Atthisstageof
development,welooklikeaFrisbee,asimpletwo-layered
disk.
HowdoesthisovalFrisbeeendupwithvonBaer’sthree
germlayersandgoontolookanythinglikeahuman?First,
cellsdivideandmove,causingtissuestofoldinon
themselves.Eventually,astissuesmoveandfold,we
becomeatubewithafoldedswellingattheheadendand
134
anotheratthetail.Ifweweretocutourselvesinhalfright
aboutnow,wewouldfindatubewithinatube.Theouter
tubewouldbeourbodywall,theinnertubeoureventual
digestivetract.Aspace,thefuturebodycavity,separates
thetwotubes.Thistube-within-a-tubestructurestayswith
usourentirelives.Theguttubegetsmorecomplicated,
withabigsacforastomachandlongintestinaltwistsand
turns.Theoutertubeiscomplicatedbyhair,skin,ribs,and
limbsthatpushout.Butthebasicplanpersists.Wemaybe
morecomplicatedthanwewereattwenty-onedaysafter
conception,butwearestillatubewithinatube,andallof
ourorgansderivefromoneofthethreelayersoftissuethat
appearedinoursecondweekafterconception.
Thenamesofthesethreeall-importantlayersare
derivedfromtheirposition:theouterlayeriscalled
ectoderm,theinnerlayerendoderm,andthemiddlelayer
mesoderm.Ectodermformsmuchoftheouterpartofthe
body(theskin)andthenervoussystem.Endoderm,the
insidelayer,formsmanyoftheinnerstructuresofthebody,
includingourdigestivetractandnumerousglands
associatedwithit.Themiddlelayer,themesoderm,forms
tissueinbetweenthegutsandskin,includingmuchofour
skeletonandourmuscles.Whetherthebodybelongstoa
salmon,achicken,afrog,oramouse,allofitsorgansare
formedbyendoderm,ectoderm,andmesoderm.
135
Ourearlydays,thefirstthreeweeksafterconception.
Wegofrombeingasinglecelltoaballofcellsandend
upasatube.
VonBaersawhowembryosrevealfundamentalpatterns
oflife.Hecontrastedtwokindsoffeaturesindevelopment:
featuressharedbyeveryspecies,andfeaturesthatvary
fromspeciestospecies.Featuressuchasthetube-withina-tubearrangementaresharedbyallanimalswitha
backbone:fish,amphibians,reptiles,birds,andmammals.
Thesecommonfeaturesappearrelativelyearlyin
development.Thefeaturesthatdistinguishus—bigger
brainsinhumans,shellsonturtles,feathersonbirds—arise
136
relativelylater.
VonBaer’sapproachisverydifferentfromthe“ontogeny
recapitulatesphylogeny”ideayoumighthavelearnedin
school.VonBaersimplycomparedembryosandnotedthat
theembryosofdifferentspecieslookedmoresimilarto
eachotherthandotheadultsofthosespecies.The
“ontogenyrecapitulatesphylogeny”approachchampioned
decadeslaterbyErnstHaeckelmadetheclaimthateach
speciestrackeditsevolutionaryhistoryasitproceeded
throughdevelopment.Accordingly,theembryoofahuman
wentthroughafish,areptile,andamammalstage.Haeckel
wouldcompareahumanembryotoanadultfishoralizard.
ThedifferencesbetweentheideasofvonBaerandHaeckel
mightseemsubtle,buttheyarenot.Inthepastone
hundredyears,timeandnewevidencehavetreatedvon
Baermuchmorekindly.Incomparingembryosofone
speciestoadultsofanother,Haeckelwascomparingapples
tooranges.Amoremeaningfulcomparisonisonewherewe
canultimatelyuncoverthemechanismsthatdrive
evolution.Forthat,wecompareembryosofonespeciesto
embryosofanother.Theembryosofdifferentspeciesare
notcompletelyidentical,buttheirsimilaritiesare
profound.Allhavegillarches,notochords,andlooklikea
tubewithinatubeatsomestageoftheirdevelopment.And,
importantly,embryosasdistinctasfishandpeoplehave
PanderandvonBaer’sthreegermlayers.
137
Atfourweeksafterconception,weareatubewithina
tubeandhavethethreegermlayersthatgiverisetoall
ourorgans.
Allofthesecomparisonsleadustotherealissueatstake.
Howdoestheembryo“know”todevelopaheadatthefront
endandananusattheback?Whatmechanismsdrive
developmentandmakecellsandtissuesabletoform
bodies?
Toanswerthesequestionsrequiredawholenew
approach.Ratherthansimplycomparingembryosasinvon
Baer’sday,wehadtofindanewwayofanalyzingthem.The
latterpartofthenineteenthcenturyusheredintheera,
138
whichwefirstdiscussedinChapter3,whenembryoswere
chopped,grafted,split,andtreatedwithvirtuallyeverykind
ofchemicalimaginable.Allinthenameofscience.
EXPERIMENTINGWITHEMBRYOS
Biologistsattheturnofthetwentiethcenturywere
grapplingwithfundamentalquestionsaboutbodies.Where
intheembryodoestheinformationtobuildthemlie?Is
thisinformationcontainedineverycellorinpatchesof
cells?Andwhatformdoesthisinformationtake—isita
specialkindofchemical?
Beginningin1903,theGermanembryologistHans
Spemannbegantoinvestigatehowcellslearnedtobuild
bodiesduringdevelopment.Hisgoalwastofindwherethe
body-buildinginformationresides.Thebigquestionfor
Spemannwaswhetherallthecellsintheembryohave
enoughinformationtobuildwholebodies,orwhetherthat
informationisconfinedtocertainpartsofthedeveloping
embryo.
Workingwithnewteggs,whichwereeasytoobtainand
relativelyeasytofiddlewithinthelab,Spemanndeviseda
cleverexperiment.Hecutoffastrandofhisinfant
daughter’shairandmadeaminiaturelassooutofit.Baby
hairisremarkablestuff;soft,thin,andpliant,itmadethe
idealmaterialfortyingupatinyspheresuchasanewtegg.
Spemanndidexactlythattoadevelopingnewtegg,
139
pinchingonesideofffromtheother.Manipulatingthe
nucleiofthecellsabit,helettheresultingcontraption
developandwatchedwhathappened.Theembryoformed
twins:twocompletesalamandersemerged,eachwitha
normalbodyplanandeachentirelyviable.Theconclusion
wasobvious:fromoneeggcancomemorethanone
individual.Thisiswhatidenticaltwinsare.Biologically,
Spemannhaddemonstratedthatintheearlyembryosome
cellshavethecapacitytoformawholenewindividualon
theirown.
Thisexperimentwasonlythebeginningofawholenew
phaseofdiscovery.
Inthe1920sHildeMangold,agraduatestudentin
Spemann’slaboratory,startedtoworkwithsmallembryos.
Thefinecontrolshehadofherfingersmadeherabletodo
someincrediblydemandingexperiments.Atthestageof
developmentwithwhichMangoldworked,thesalamander
embryoisasphereaboutasixteenthofaninchindiameter.
Sheloppedoffatinypieceoftissue,smallerthanapinhead,
fromonepartoftheembryoandgrafteditontotheembryo
ofanotherspecies.WhatMangoldtransplantedwasn’tjust
anypatch,butanareawherecellsthatweretoformmuch
ofthethreegermlayersweremovingandfolding.Mangold
wassoskilledthatthegraftedembryosactuallycontinued
todevelop,givingherapleasantsurprise.Thegraftedpatch
ledtotheformationofawholenewbody,includingaspinal
cord,back,belly,evenahead.
140
Justbymovingasmallpatchoftissueintheembryo,
Mangoldproducedtwins.
Whyisallthisimportant?Mangoldhaddiscovereda
smallpatchoftissuethatwasabletodirectothercellsto
formanentirebodyplan.Thetiny,incrediblyimportant
patchoftissuecontainingallthisinformationwastobe
knownastheOrganizer.
Mangold’sdissertationworkwasultimatelytowinthe
NobelPrize,butnotforher.HildeMangolddiedtragically
(thegasolinestoveinherkitchencaughtfire)beforeher
thesiscouldevenbepublished.SpemannwontheNobel
PrizeinMedicinein1935,andtheawardcites“his
discoveryoftheOrganizeranditseffectinembryonic
development.”
Today,manyscientistsconsiderMangold’sworktobe
thesinglemostimportantexperimentinthehistoryof
embryology.
AtroughlythesametimethatMangoldwasdoing
experimentsinSpemann’slab,W.Vogt(alsoinGermany)
wasdesigningclevertechniquestolabelcells,orbatchesof
them,andthusallowtheexperimentertowatchwhat
happensastheeggdevelops.Vogtwasabletoproducea
141
mapoftheembryothatshowswhereeveryorgan
originatesintheegg.Weseetheantecedentsofthebody
planinthecellfatesoftheearlyembryo.
Fromtheearlyembryologists,peoplelikevonBaer,
Pander,Mangold,andSpemann,wehavelearnedthatallthe
partsofouradultbodiescanbemappedtoindividual
batchesofcellsinthesimplethree-layeredFrisbee,andthe
generalstructureofthebodyisinitiatedbytheOrganizer
regiondiscoveredbyMangoldandSpemann.
Cut,slice,anddice,andyou’llfindthatallmammals,
birds,amphibians,andfishhaveOrganizers.Youcaneven
sometimesswaponespecies’Organizerforanother.Take
theOrganizerregionfromachickenandgraftittoa
salamanderembryo:yougetatwinnedsalamander.
ButjustwhatisanOrganizer?Whatinsideittellscells
howtobuildbodies?DNA,ofcourse.AnditisinthisDNA
thatwewillfindtheinnerrecipethatwesharewiththerest
ofanimallife.
OFFLIESANDMEN
VonBaerwatchedembryosdevelop,comparedonespecies
toanother,andsawfundamentalpatternsinbodies.
MangoldandSpemannphysicallydistortedembryosto
learnhowtheirtissuesbuildbodies.IntheDNAage,wecan
askquestionsaboutourowngeneticmakeup.Howdoour
genescontrolthedevelopmentofourtissuesandour
142
bodies?Ifyoueverthoughtthatfliesareunimportant,
considerthis:mutationsinfliesgaveusimportantcluesto
themajorbodyplangenesactiveinhumanembryos.We
putthiskindofthinkingtouseinthediscoveryofgenes
thatbuildfingersandtoes.Nowwe’llseehowittellsus
aboutthewaysentirebodiesarebuilt.
Flieshaveabodyplan.Theyhaveafrontandaback,atop
andabottom,andsoon.Theirantennae,wings,andother
appendagespopoutofthebodyintherightplace.Except
whentheydon’t.Somemutantflieshavelimbsgrowingout
oftheirheads.Othershaveduplicatewingsandextrabody
segments.Theseareamongtheflymutantsthattelluswhy
ourvertebraechangeshapefromtheheadendtotheanal
endofthebody.
Peoplehavebeenstudyingabnormalfliesforovera
hundredyears.Mutantswithoneparticularkindof
abnormalitygotspecialattention.Theseflieshadorgansin
thewrongplaces—alegwhereanantennashouldhave
been;anextrasetofwings—orweremissingbody
segments.Somethingwasmessingwiththeirfundamental
bodyplan.Ultimately,thesemutantsarisefromsomesort
oferrorintheDNA.Rememberthatgenesarestretchesof
DNAthatlieonthechromosome.Usingavarietyof
techniquesthatallowustovisualizethechromosome,we
canidentifythepatchofthechromosomeresponsiblefor
themutanteffect.Essentially,webreedmutantstomakea
wholepopulationwhereeveryindividualhasthegenetic
error.Then,usingavarietyofmolecularmarkers,we
143
comparethegenesofindividualswiththemutationto
thosewithout.Thisallowsustopinpointtheregionandthe
likelystretchofchromosomeresponsibleforthemutant
effect.Itturnsoutthataflyhaseightgenesthatmakesuch
mutants.Thesegeneslienexttooneanotherononeofthe
longDNAstrandsofthefly.Thegenesthataffectthehead
segmentslienexttothosethataffectthesegmentsinthe
middleofthefly,thepartofthebodythatcontainsthe
wings.ThesebitsofDNA,inturn,lieadjacenttotheones
thatcontrolthedevelopmentoftherearpartofthefly.
Thereisawonderfulordertothewaythegenesare
organized:theirpositionalongtheDNAstrandparallelsthe
structureofthebodyfromfronttoback.
Nowthechallengewastoidentifythestructureofthe
DNAactuallyresponsibleforthemutation.MikeLevineand
BillMcGinnis,inWalterGehring’slabinSwitzerland,and
MattScott,inTomKauffman’slabinIndiana,noticedthatin
themiddleofeachgenewasashortDNAsequencethatwas
virtuallyidenticalineachspeciestheylookedat.Thislittle
sequenceiscalledahomeobox.Theeightgenesthat
containthehomeoboxarecalledHoxgenes.Whenthe
scientistsfishedaroundforthisgenesequenceinother
species,theyfoundsomethingsouniformthatitcameasa
truesurprise:versionsoftheHoxgenesappearinevery
animalwithabody.
144
Hoxgenesinfliesandpeople.Thehead-to-tail
organizationofthebodyisunderthecontrolof
differentHoxgenes.Flieshaveonesetofeighthox
genes,eachrepresentedasalittleboxinthediagram.
Humanshavefoursetsofthesegenes.Infliesand
145
people,theactivityofagenematchesitspositionon
theDNA:genesactiveintheheadlieatoneend,those
inthetailatanother,withgenesaffectingthemiddleof
thebodylyinginbetween.
Versionsofthesamegenessculptthefront-to-back
organizationofthebodiesofcreaturesasdifferentasflies
andmice.MesswiththeHoxgenesandyoumesswiththe
bodyplaninpredictableways.Ifyoumakeaflythatlacksa
geneactiveinamiddlesegment,themidsectionoftheflyis
missingoraltered.Makeamousethatlacksoneofthe
genesthatspecifiesthoracicsegments,andyoutransform
partsoftheback.
Hoxgenesalsoestablishtheproportionsofourbodies—
thesizesofthedifferentregionsofourhead,chest,and
lowerback.Theyareinvolvedinthedevelopmentof
individualorgans,limbs,genitalia,andguts.Changesin
thembringaboutchangesinthewaysourbodiesareput
together.
Differentkindsofcreatureshavedifferentnumbersof
Hoxgenes.Fliesandotherinsectshaveeight,miceand
othermammalsthirty-nine.Thethirty-nineHoxgenesin
miceareallversionsoftheonesthatarefoundinflies.This
similarityhasledtotheideathatthelargenumberof
mammalianHoxgenesarosefromaduplicationofthe
smallercomplementofgenesinthefly.Despitethese
differencesinnumber,themousegenesareactivefrom
fronttobackinaverypreciseorderjustastheflygenesare.
Canwegoevendeeperinourfamilytree,findingsimilar
146
stretchesofDNAinvolvedinmakingevenmore
fundamentalpartsofourbodies?Theanswer,surprisingly,
isyes.Anditlinksustoanimalsevensimplerthanflies.
DNAANDTHEORGANIZER
AtthetimewhenSpemannwontheNobelPrize,the
Organizerwasalltherage.Scientistssoughtthemysterious
chemicalthatcouldinducetheentirebodyplan.Butjustas
popularculturehasyo-yosandTickleMeElmodolls,so
sciencehasfadsthatwaxandwane.Bythe1970s,the
Organizerwasviewedaslittlemorethanacuriosity,a
cleveranecdoteinthehistoryofembryology.Thereason
forthisfallfromgracewasthatnoonecoulddecipherthe
mechanismsthatmadeitwork.
ThediscoveryofHoxgenesinthe1980schanged
everything.Intheearly1990s,whentheOrganizerconcept
wasstilldecidedlyunfashionable,EddieDeRobertis’s
laboratoryatUCLAwaslookingforHoxgenesinfrogs,using
techniqueslikeLevineandMcGinnis’s.Thesearchwas
broadanditnettedmanydifferentkindsofgenes.Oneof
thesehadaveryspecialpatternofactivity.Itwasactiveat
theexactsiteintheembryothatcontainstheOrganizer,
anditwasactiveatexactlytherighttimeofdevelopment.I
canonlyimaginewhatDeRobertisfeltwhenhefoundthat
gene.HewaslookingattheOrganizer,andthereinthe
Organizerwasagenethatseemedspecificallytocontrolit
147
orbelinkedtoitsactivityintheembryo.TheOrganizerwas
back.
Organizergenesstartedpoppingupinlaboratories
everywhere.Whiledoingadifferentkindofexperiment,
RichardHarlandatBerkeleyfoundanothergene,whichhe
calledNoggin.NoggindoesexactlywhatanOrganizergene
should.WhenHarlandtooksomeNogginandinjecteditinto
therightplaceinanembryo,itfunctionedexactlylikethe
Organizer.Theembryodevelopedtwobodyaxes,including
twoheads.
AreDeRobertis’sgeneandNoggintheactualbitsofDNA
thatmakeuptheOrganizer?Theanswerisyesandno.
Manygenes,includingthesetwo,interacttoorganizethe
bodyplan.Suchsystemsarecomplex,becausegenescan
playmanydifferentrolesduringdevelopment.Noggin,for
example,playsaroleinthedevelopmentofthebodyaxis
butisalsoinvolvedwithahostofotherorgans.
Furthermore,genesdonotactalonetospecifycomplicated
cellbehaviorslikethoseweseeinheaddevelopment.Genes
interactwithothergenesatallstagesofdevelopment.One
genemayinhibittheactivityofanotherorpromoteit.
Sometimesmanygenesinteracttoturnanothergeneonor
off.Fortunately,newtoolsallowustostudytheactivityof
thousandsofgenesinacellatonce.Couplethistechnology
withnewcomputer-basedwaysofinterpretinggene
functionandwehaveenormouspotentialtounderstand
howgenesbuildcells,tissues,andbodies.
Understandingthesecomplexinteractionsbetween
148
batteriesofgenesshedslightontheactualmechanisms
thatbuildbodies.Nogginservesasagreatexample.Noggin
alonedoesnotinstructanycellintheembryoaboutits
positiononthetop–bottomaxis;rather,itactsinconcert
withseveralothergenestodothis.Anothergene,BMP-4,is
abottomgene;itisturnedonincellsthatwillmakethe
bottom,orbellyside,ofanembryo.Thereisanimportant
interactionbetweenBMP-4andNoggin.WhereverNogginis
active,BMP-4cannotdoitsjob.TheupshotisthatNoggin
doesnottellcellstodevelopas“cellsonthetopofthe
body”instead,itturnsoffthesignalthatwouldmakethem
bottomcells.Theseoff-oninteractionsunderlievirtuallyall
developmentalprocesses.
ANINNERSEAANEMONE
Itisonethingtocompareourbodieswiththoseoffrogs
andfish.Inarealsenseweandtheyaremuchalike:weall
haveabackbone,twolegs,twoarms,ahead,andsoon.
Whatifwecompareourselveswithsomethingutterly
different,forexamplejellyfishandtheirrelatives?
Mostanimalshavebodyaxesdefinedbytheirdirection
ofmovementorbywheretheirmouthandanuslierelative
toeachother.Thinkaboutit:ourmouthisontheopposite
endofthebodyfromouranusand,asinfishandinsects,it
isusuallyinthedirection“forward.”
Howcanwetrytoseeourselvesinanimalsthathaveno
149
nervecordatall?Howaboutnoanusandnomouth?
Creatureslikejellyfish,corals,andseaanemoneshavea
mouth,butnoanus.Theopeningthatservesasamouth
alsoservestoexpelwaste.Whilethatoddarrangement
maybeconvenientforjellyfishandtheirrelatives,itgives
biologistsvertigowhentheytrytocomparethesecreatures
toanythingelse.
Anumberofcolleagues,MarkMartindaleandJohn
Finnertyamongthem,havedivedintothisproblemby
studyingthedevelopmentofthisgroupofanimals.Sea
anemoneshavebeenremarkablyinformative,becausethey
arecloserelativesofjellyfishandtheyhaveaveryprimitive
bodypattern.Also,seaanemoneshaveaveryunusual
shape,onethatatfirstglancewouldseemtomakethem
worthlessasaformtocomparetous.Aseaanemoneis
shapedlikeatreetrunkwithalongcentralstumpanda
bunchoftentaclesattheend.Thisoddshapemakesit
particularlyappealing,sinceitmighthaveafrontanda
back,atopandabottom.Drawalinefromthemouthtothe
baseoftheanimal.Biologistshavegiventhatlineaname:
theoral–aboralaxis.Butnamingitdoesn’tmakeitmore
thananarbitraryline.Ifitisreal,thenitsdevelopment
shouldresemblethedevelopmentofoneofourownbody
dimensions.
Martindaleandhiscolleaguesdiscoveredthatprimitive
versionsofsomeofourmajorbodyplangenes—thosethat
determineourhead-to-anusaxis—areindeedpresentin
theseaanemone.And,moreimportant,thesegenesare
150
activealongtheoral–aboralaxis.Thisinturnmeansthat
theoral–aboralaxisoftheseprimitivecreaturesis
geneticallyequivalenttoourhead-to-anusaxis.
Oneaxisdown,anothertogo.Doseaanemoneshave
anythinganalogoustoourbelly-to-backaxis?Sea
anemonesdon’tseemtohaveanythingcomparable.
Despitethis,Martindaleandhiscolleaguestookthebold
stepofsearchingintheseaanemoneforthegenesthat
specifyourbelly-to-backaxis.Theyknewwhatourgenes
lookedlike,andthisgavethemasearchimage.They
uncoverednotone,butmanydifferentbelly-to-backgenes
intheseaanemone.Butalthoughthesegeneswereactive
alonganaxisintheseaanemone,thataxisdidn’tseemto
correlatewithanypatterninhowtheadultanimal’sorgans
areputtogether.
151
Jellyfishrelatives,suchasseaanemones,haveafront
andabackaswedo,abodyplansetupbyversionsof
thesamegenes.
Justwhatthishiddenaxiscouldbeisnotapparentfrom
theoutsideoftheanimal.Ifwecutoneinhalf,however,we
findanimportantclue,anotheraxisofsymmetry.Calledthe
directiveaxis,itseemstodefinetwodistinctsidesofthe
creature,almostaleftandaright.Thisobscureaxiswas
knowntoanatomistsbackinthe1920sbutremaineda
curiosityinthescientificliterature.Martindale,Finnerty,
andtheirteamchangedthat.
Allanimalsarethesamebutdifferent.Likeacakerecipe
passeddownfromgenerationtogeneration—with
enhancementstothecakeineach—therecipethatbuilds
ourbodieshasbeenpasseddown,andmodified,foreons.
Wemaynotlookmuchlikeseaanemonesandjellyfish,but
therecipethatbuildsusisamoreintricateversionofthe
onethatbuildsthem.
Powerfulevidenceforacommongeneticrecipefor
animalbodiesisfoundwhenweswapgenesbetween
species.Whathappenswhenyouswapabody-building
genefromananimalthathasacomplexbodyplanlikeours
withonefromaseaanemone?RecallthegeneNoggin,
whichinfrogs,mice,andhumansisturnedoninplacesthat
willdevelopintobackstructures.Injectextraamountsof
frogNogginintoafrogegg,andthefrogwillgrowextra
backstructures,sometimesevenasecondhead.Insea
anemoneembryos,aversionofNogginisalsoturnedonat
152
oneendofthedirectiveaxis.Now,themillion-dollar
experiment:taketheproductofNogginfromasea
anemoneandinjectitintoafrogembryo.Theresult:afrog
withextrabackstructures,almostthesameresultasifthe
frogwereinjectedwithitsownNoggin.
Now,though,aswegobackintime,weareleftwithwhat
lookslikeahugegap.Everythinginthischapterhadabody.
Howdowecompareourselveswiththingsthathaveno
bodiesatall—withsingle-celledmicrobes?
153