Kalthoff / Second Edition Contents

ANALYSIS OF BIOLOGICAL DEVELOPMENT, second edition Klaus Kalthoff / University of Texas

DETAILED TABLE OF O!TE!T" # Basic Principles) ( Key Strategies)
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The Principle of Epigenesis De elop!ental Periods and Stages in the "ife Cycle E!#ryonic De elop!ent Begins $ith %ertili&ation and Ends $ith the Co!pletion of 'istogenesis Poste!#ryonic De elop!ent Can Be Direct or (ndirect )d*lthood Begins $ith the +nset of ,eprod*ction and Ends $ith Death Classical )nalytical Strategies in De elop!ental Biology E!#ryonic Cells 'a e Predicta#le %ates in De elop!ent )nalysis of De elop!ent ,e.*ires a Strategy of Controlled (nterference (solation/ ,e!o al and Transplantation of E!#ryonic Parts )re Key Strategies of E!#ryologists 1enetic )nalysis of De elop!ent ,ed*ctionist and Synthetic )nalyses of De elop!ent + / T$E &OLE OF ELL" I! DE)ELO%*E!T

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The Principle of Cell*lar Contin*ity The Cell and (ts +rganelles Cell Shape and the Cytos3eleton Cells Change Their E4ternal Shape )s 5ell )s Their (nternal +rder 6icrot*#*les 6aintain Cell Shape and 6ediate (ntracell*lar Transport 6icrofila!ents 1enerate Contracting %orces and Sta#ili&e the Cell S*rface (nter!ediate %ila!ents 7ary )!ong Different Cell Types The Cell Cycle and (ts Control Chro!oso!es )re D*plicated D*ring S Phase Chro!oso!e D*plicates )re Split #et$een Da*ghter Cells D*ring 6itosis The Cell Cytoplas! (s Di ided D*ring Cyto3inesis The Cyclic )cti ity of a Protein Co!ple4 Controls the Cell Cycle Cell 6e!#ranes Cell*lar 6o e!ent Cell :*nctions in Epithelia and 6esenchy!e Cell*lar Signaling (ntercell*lar Signals 7ary $ith ,espect to Distance/ Speed of )ction/ and Co!ple4ity 6e!#rane ,eceptors (nitiate Different Signaling Path$ays )denylate Cyclase 1enerates c)6P as a Second 6essenger Phospholipase C< 1enerates Diacylglycerol/ (nositol Trisphosphate/ and Calci*! (ons as Second 6essengers

Kalthoff / Second Edition Contents

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The ,TK<,as<E,K Path$ay )cti ates Transcription %actors Signal Transd*ction Path$ays )re "in3ed $ith +ne )nother and 5ith Cell )dhesion Concl*sion and +*tloo3

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The Disco ery of the 6a!!alian Egg The 1er! "ine Concept and the D*al +rigin of 1onads 6eiosis 'o!ologo*s Chro!oso!es )re Separated d*ring 6eiosis The Ti!ing of 6eiosis Differs #et$een 6ales and %e!ales 6eiosis Pro!otes 1enetic 7ariation/ 'elps to Esta#lish 'o!o&ygo*s 6*tant )lleles/ and Eli!inates Bad 1enes -.0 Sper!atogenesis 6ale 1er! Cells De elop in Se!inifero*s T*#*les Sper!iogenesis Sper!atogonia Beha e as Ste! Cells -.2 +ogenesis +ocytes )re S*pplied $ith "arge )!o*nts of ,>) ?ol3 Proteins for +ocytes )re Synthesi&ed in the "i er or %at Body The + arian )*tono!y (!poses Polarity on the +ocyte 6at*ration Processes Prepare the +ocyte for + *lation and %ertili&ation Eggs )re Protected #y Different Types of En elopes @*ethod ,.' Autoradio/ra0hy 1 / FE&TILI2ATIO!

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(nteractions Before Sper!<Egg )dhesion 6any Sper! )re )ttracted to Eggs #y Che!ical Signals So!e Sper! 6*st Andergo Capacitation Before They Can %ertili&e Eggs %ertili&ation in Sea Archins Sea Archin Sper! Andergo the )croso!e ,eaction Before They )dhere to the 7itelline En elope Sea Archin Sper! )dhere to Eggs $ith an )croso!al Protein Called Bindin 1a!ete %*sion "eads to the %or!ation of a %ertili&ation Cone %ertili&ation in 6a!!als 6o*se Sper! Andergo the )croso!e ,eaction )fter They )dhere to the Sona Pell*cida ) Bioassay (s a Po$erf*l Strategy to ,e eal a Biologically )cti e Co!ponent 6o*se Sper! )dhere to a Specific Bona Pell*cida Protein )nti#odies to Sper!<Egg )dhesion Proteins Can )ct as Contracepti es Egg )cti ation Egg )cti ation 6ay Be Triggered #y Different Signaling 6echanis!s ) Te!porary ,ise in Ca2C Concentration is %ollo$ed #y )cti ation of Protein Kinase C )cti ation )ccelerates The EggDs 6eta#olis! in Preparation for Clea age Bloc3s to Polysper!y The %ertili&ation Potential Ser es as a %ast Bloc3 to Polysper!y The Cortical ,eaction Ca*ses a Slo$ Bloc3 to Polysper!y

Kalthoff / Second Edition Contents

4.6 The Principle of Synergistic 6echanis!s 0.9 Parthenogenesis 3*ethod 1., I44unostainin/ 5/

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?ol3 Distri#*tion and Clea age Pattern Clea age Patterns of ,epresentati e )ni!als Sea Archins 'a e (solecithal Eggs and Andergo 'olo#lastic Clea age )!phi#ians 'a e 6esolecithal Eggs #*t Still Clea e 'olo#lastically Snails 'a e (solecithal Eggs and %ollo$ a Spiral Clea age Pattern The )scidian Clea age Pattern (s Bilaterally Sy!!etrical 6a!!alian Eggs Sho$ ,otational Clea age Eggs 5ith 7aria#le Clea age Sho$ ,eg*lati e De elop!ent Birds/ ,eptiles/ and 6any %ishes 'a e Telolecithal Eggs and Andergo Discoidal Clea age (nsects 'a e Centrolecithal Eggs and Andergo S*perficial Clea age Spatial Control of Clea ageE Positioning and +rientation of 6itotic Spindles )ctin and 6yosin %or! the Contractile ,ing in Cyto3inesis The 6itotic Spindle )4is Deter!ines the +rientation of the Clea age Plane 6echanical Constraints 6ay +rient 6itotic Spindles Centroso!es +rgani&e 6itotic Spindles in ,eg*lar 5ays D*ring Clea age Specific Sites in the Egg Corte4 )ttract and )nchor Centroso!es 6aternal 1ene Prod*cts 6ay +rient 6itotic Spindles The Ti!ing of Clea age Di isions The Cell Cycle Slo$s Do$n d*ring the 6id#last*la Transition (6BT) Stage< and ,egion< Specific 1ene )cti ities 6od*late the Basic Cell Cycle )fter 6BT The >*cleocytoplas!ic ,atio 6ay Trigger 6BT )ccording to a Titration 6odel 6 / ELL FATE, %OTE! (, A!D DETE&*I!ATIO!

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%ate 6apping Conal )nalysis Potency of E!#ryonic Cells Deter!ination of E!#ryonic Cells Cell Deter!ination (s Disco ered Thro*gh +perational Criteria Drosophila Blastoder! Cells )re Deter!ined to %or! Str*ct*res $ithin a Single Seg!ent Drosophila Cells )re Born $ith a Bias that is 'oned #y

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S*#se.*ent (nteractions Prospecti e >e*ral Plate Cells of )!phi#ians )re Deter!ined D*ring 1astr*lation 6o*se E!#ryonic Cells )re >ot Deter!ined Antil the Blastocyst Stage 8.2 Properties of the Deter!ined State Deter!ination (s a Step$ise Process of (nstr*ction and Co!!it!ent Cell Deter!ination +cc*rs as Part of E!#ryonic Pattern %or!ation The Deter!ined State (s ()l!ost) Sta#ly Passed +n d*ring 6itosis 8.8 ,eg*lation in De elop!ent 3*ethod 6.' La7elin/ ells 7y "o4atic rossover

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Theories of Cell Differentiation +#ser ation on Cells Cells 6ay Carry +*t Different %*nctions at Different Ti!es Cells Change Their Differentiated State D*ring ,egeneration +#ser ations on Chro!oso!es Different Cells fro! the Sa!e (ndi id*al Sho$ the Sa!e Set of Chro!oso!es Polytene Chro!oso!es Sho$ the Sa!e Banding Pattern in Different Tiss*es Chro!oso!e Eli!ination (s )ssociated $ith the Dichoto!y #et$een 1er! "ine and So!atic Cells 6olec*lar Data on 1eno!ic E.*i alence Totipotency of Differentiated Plant Cells Totipotency of >*clei fro! E!#ryonic )ni!al Cells >e$t Blasto!eres De elop >or!ally after Delayed >*cleation >*clei fro! E!#ryonic Cells )re Still Totipotent Pl*ripotency of >*clei fro! Differentiated )ni!al Cells >*clei fro! +lder Donor Cells Sho$ a Decreasing )#ility to Pro!ote the De elop!ent of a >e$ +rganis! >*clei fro! 6at*re Cells )re Anprepared for the %ast 6itotic Cycles of Early %rog E!#ryos So!e Differentiated Cells Contain 'ighly Pl*ripotent >*clei 6a!!als Can Be Cloned #y %*sing %etal or )d*lts Cells $ith En*cleated Eggs >*clear Transfer E4peri!ents $ith 6a!!als 'a e (!portant )pplications in Science/ )gric*lt*re/ and 6edicine 5ill '*!ans #e Cloned in the %*t*reF Control of >*clear )cti ities #y the Cytoplas!ic En iron!ent 1ene E4pression Changes *pon Transplantation of >*clei to >e$ Cytoplas!ic En iron!ents Cell %*sion E4poses >*clei to >e$ Cytoplas!ic Signals Concl*sion and +*tloo3

Kalthoff / Second Edition Contents

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: / LO ALI2ED (TO%LA"*I DETE&*I!A!T"

8.1 ;.2 ;.-

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The Principle of Cytoplas!ic "ocali&ation Polar "o#e %or!ation as a 6eans of Cytoplas!ic "ocali&ation 1er! Cell Deter!inants in (nsects Eggs ,esc*e E4peri!ents Can ,estore Defecti e E!#ryos to >or!al De elop!ent 'eterotopic Transplantation Tests Cytoplas!ic Deter!inants for )cti ity in )#nor!al "ocations "ocali&ation of Polar 1ran*les ,e.*ires ,>) Transport )long 6icrot*#*les Bicoid !,>) in Drosophila Eggs 6yoplas! in )scidian Eggs Cytoplas!ic Co!ponents of )scidian Eggs )re Segregated Apon %ertili&ation 6yoplas! is >ecessary and S*fficient for Tail 6*scle %or!ation 6yoplas! Segregation (n ol es a Plas!a 6e!#rane "a!ina 6yoplas! is )ssociated $ith "ocali&ed 6aternal ,>)s Cytoplas!ic "ocali&ation at )d anced E!#ryonic Stages Bioassays for "ocali&ed Cytoplas!ic Deter!inants The Principle of Defa*lt Progra!s Properties of "ocali&ed Cytoplas!ic Deter!inants Cytoplas!ic Deter!inants Control Certain Cell "ineages or Entire Body ,egions "ocali&ed Cytoplas!ic Deter!inants 6ay Be )cti ating or (nhi#itory Cytoplas!ic "ocali&ation 6ay or 6ay >ot Be )ssociated $ith 7isi#le 6ar3ers 6ost "ocali&ed Cytoplas!ic Deter!inants )re 6aternal !,>)s Cytoplas!ic +rgani&ation +cc*rs at Different Stages of De elop!ent Asing 7ario*s Cell*lar 6echanis!s ; / A<I" FO&*ATIO! A!D *E"ODE&* I!DU TIO!

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Body )4es and Planes 1eneration of ,hi&oid<Thall*s )4is in %*c*s Deter!ination of the )ni!al<7egetal )4is in )!phi#ians The )ni!al<7egetal )4is +riginates #y +riented Transport d*ring +ogenesis The )ni!al<7egetal Polarity Deter!ines the Spatial +rder of the 1er! "ayers 7egetal Blasto!eres (nd*ce Their )ni!al >eigh#ors to %or! 6esoder! The Principle of (nd*ction Deter!ination of the Dorso entral )4is in )!phi#ians

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Deep Cytoplas! Andergoes ,eg*lar 6o e!ents d*ring Egg )cti ation Cytoplas!ic ,earrange!ents %ollo$ing %ertili&ation (n ol e Cortical ,otation 6icrot*#*les 6o e Cytoplas!ic Co!ponents Dorsally Beyond Cortical Displace!ent ) Dorsali&ing )cti ity 6o es fro! the 7egetal Pole to the Dorsal Side D*ring Cortical ,otation Dorsal 7egetal and E.*atorial Blasto!eres ,esc*e 7entrali&ed E!#ryos Effect of Dorso entral Polarity on 6esoder! (nd*ction in Xenopus 6esoder! is (nd*ced $ith a ,*di!entary Dorso entral Pattern Dorsal 6arginal Cells (nd*ce an )rray of 6esoder!al +rgan ,*di!ents 6olec*lar 6echanis!s of Dorso entral )4is %or!ation and 6esoder! (nd*ction <Catenin 6ay Specify Dorso entral Polartiy Se eral 1ro$th %actors 'a e 6esoder!<(nd*cing )cti ity T1%< 6e!#ers and B<Catenin 6ay )ct Synergistically in (nd*cing Spe!annDs +rgani&er Deter!ination of "eft<,ight )sy!!etry

ha0ter '= / -astulation 1G.1 The )nalysis of 6orphogenesis 6orphogenesis (n ol es Typical Epithelial 6o e!ents 6orphogenesis (s Based on a S!all ,epertoire of Cell )cti ities 1astr*lation in Sea Archins 1astr*lation in )!phi#ians Different 1astr*la )reas Sho$ Distinct Cell*lar Beha iors Bottle Cells 1enerate the (nitial Depression of the Blastopore Deep 6arginal Bone Cells )re >ecessary for (n ol*tion Deep Bone Cells and (n ol*ting 6arginal Bone Cells 6igrate on the (nside of the Blastocoel ,oof Con ergent E4tension (s Especially Strong in the Dorsal 6arginal Bone )ni!al Cap and >onin ol*ting 6arginal Bone Andergo Epi#oly 'o$ )re Patterns of Cell Beha ior ,elated to 1ene E4pressionF 1astr*lation in %ishes and Birds Be#rafish E!#ryos De elop fro! T$o Cell "ayers 6ostly #y Con ergent E4tension Chic3en E!#ryos De elop %ro! +ne Cell "ayer 6ostly #y (ngression 1astr*lation in '*!ans '' / ELL AD$E"IO! A!D *O&%$O-E!E"I"

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11.1

Cell )ggregation St*dies in Vitro Cells fro! Different Tiss*es )dhere to +ne )nother Selecti ely Tiss*es %or! 'ierarchies of )dhesi eness 11.2 Cell )dhesion 6olec*les (!!*noglo#*linli3e C)6s 6ay )llo$ or 'inder Cell )dhesion Cadherins 6ediate C)2C H Dependent Cell )dhesion "ectins Bind 'eterot*pically to S*gar ,esid*es 11.EC6 6olec*les and Their Cell*lar ,eceptors 1lycosa!inopglycans and Proteoglycans %or! and )!orpho*s/ 'ydrophilic 1ro*nd S*#stance %i#ro*s 1lycoproteins 6a3e Ap the Dyna!ic 6esh$or3 of the EC6 (ntegrins 6ediate Cell )dhesion to EC6 6olec*les 11.0 The ,ole of Cell and S*#strate )dhesion 6olec*les in 6orphogenesis C)6 E4pression is Correlated $ith Cell %ates Cell )dhesi eness Changes d*ring Sea Archin 1astr*lation C)6s %acilitate the %or!ation of Cell :*nctions %i#ro*s EC6 Co!ponents Pro ide Contact 1*idance to Cells )!phi#ian 1astr*lation ,e.*ires %i#ronectin on the (nner S*rface of the Blastocoel ,oof 11.2 6orphoreg*latory ,oles of Cell and S*#strate )dhesion 6olec*les C)6 and S)6 1enes )re Controlled #y Selector 1enes Cell<Cell )dhesion and Cell<S*#strat*! (nteractions )ffect 1ene )cti ity 3 *ethods ''.' Isolatin/ ell Adhesion *olecules and Their -enes >ith Anti7odies '+ / !EU&ULATIO! A!D A<I" I!DU TIO!

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>e*r*lation as an E4a!ple of +rganogenesis >e*r*lation (s of Scientific and 6edical (nterest >e*r*lation in )!phi#ians +cc*rs in T$o Phases >e*ral T*#es of Bird E!#ryos 'a e 'inges (n '*!ans/ >e*ral T*#e Clos*re Begins in the >ec3 ,egion (n %ish/ the >e*ral T*#e +riginates as a Solid ,od 6echanis!s of >e*r*lation in )!phi#ians >e*r*lation Depends on Tiss*es )dIacent to the >e*ral Plate >e*ral Plate Cells Andergo Col*!ni&ation (ntercalation of >er*al Plate Cells Ca*ses Con ergent E4tension Both Col*!nari&ation and Cell (ntercalation Contri#*te to 1enerating the Keyhole Shape >e*ral T*#e Clos*re (s )ssociated $ith )pical Constriction/ ,apid )nteroposterior E4tension/ and Cell Cra$ling The ,ole of (nd*ction in )4is %or!ation The Dorsal Blastopore "ip +rgani&es the %or!ation of an Entire E!#ryo Does the +rgani&er 'a e Str*ct*reF )4is (nd*ction Sho$s ,egional Specificity

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6echanis!s of >e*ral (nd*ction There )re T$o Signaling Path$aysJPlanar and 7erticalJfor >e*ral (nd*ction Planar (nd*ction Plays a 6aIor ,ole in Xenopus E!#ryos >e*ral (nd*ction is a 6*ltistep Process )4is (nd*ction #y Disinhi#ition Dorsal De elop!ent +cc*rs as a Defa*lt Progra! in Xenopus Spe!annDs +rgani&er (nacti ates a 7entrali&ing Signal Basic K*estions are Still Anresol ed ', / E TODE&*AL O&-A!"

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>e*ral T*#e >er o*s Tiss*e Consists of >e*rons and 1lial Cells The Spinal Cord (s Patterned #y Signal fro! )dIacent Tiss*es The Basic +rgani&ation of the Spinal Cord (s 6odified in the Brain The Peripheral >er o*s Syste! is of Di erse +rigin >e*ral Crest >C Cells )rise at the Bo*ndary Bet$een >e*ral Plate and Epider!is >C Cells 'a e Different 6igration ,o*tes and a 5ide ,ange of %ates The Strategy of Clonal )nalysis Sho$s that >C Cells )re a 'eterogeneo*s Pop*lation of Pl*ripotent Cells The Strategies of 'eterotopic and 'eterochronic Transplantation ,e eal Spatial and Te!poral ,estrictions to >C Cell 6igration E4tracell*lar 6atri4 )ffects the Deter!ination of >C Cells ,egion<Specific 1ro$th %actors )re (n ol ed in >C Cell Deter!ination Ectoder!al Placodes The +tic Placode %or!s the (nner Ear The "ens Placode De elops Together $ith the ,etina >asal Placodes %or! +lfactory Sensory Epithelia Epider!is '1 / E!DODE&*AL A!D *E"ODE&*AL O&-A!"

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Endoder!al Deri ati es The E!#ryonic Pharyn4 Contains a Series of )rches E!#ryos Pass thro*gh a Phylotypic Stage after +rganogenesis The Endoder! "ines the (nside of the (ntestine and (ts )ppendages )4ial and Para4ial 6esoder! )4ial 6esoder! %or!s the Prechordal Plate and the >otochord Para4ial 6esoder! %or!s the Preso!itic Plates and So!ites

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10.0 14.5 10.8

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So!ites )re Patterned #y Signal fro! S*rro*nding +rgan ,*di!ents Connecti e Tiss*e and S3eletal 6*scle Connecti e Tiss*e Contains "arge )!o*nts of E4tracell*lar 6atri4 S3eletal 6*scle %i#ers )rise Thro*gh Cell %*sion (nter!ediate 6esoder! The Principle of ,eciprocal (nteraction "ateral Plates The "ateral Plates S*rro*nd the Coelo!ic Ca ities The Cardio asc*lar Syste! De elops fro! 7ario*s 6esoder!al Prec*rsors Cardio asc*lar Syste! De elop!ent ,ecapit*lates the Phylotopic Stage S!ooth 6*scle Consists of Single Cells E4trae!#ryonic 6e!#ranes The )!nion and Chorion )re %or!ed #y "ayers of Ectoder! and 6esoder! The ?ol3 Sac and )llantois )re %or!ed #y "ayers of Endoder! and 6esoder! The 6a!!alian Placenta (s %or!ed fro! the E!#ryonic Tropho#last and the Aterine Endo!etri*! U"E OF *UTA!T" A!D T&A!"-E!I O&-A!I"*" I! T$E A!AL("I" OF

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The 'istorical Separation of 1enetics fro! De elop!ental Biology 6odern 1enetic )nalysis of De elop!ent 6*tants ,e eal the 'idden L"ogicM of E!#ryonic De elop!ent Drosophila 6*tants )llo$ the )nalysis of a Co!ple4 Body Pattern Caenorhabditis elegans 6*tants Anco er 1ene )cti ities Controlling the Cell "ineages 1enetic )nalysis of the 6o*se Mus musculus Ases E!#ryonic Ste! Cells The Be#ra %ish Danio rerio is 1enetically Tracta#le and S*ita#le for Cell Transplantation 1enetic )nalysis ,e eals Si!ilarity of Plant and )ni!al De elop!ent D>) Cloning and Se.*encing D>) Can Be ,eplicated/ Transcri#ed/ and ,e erse< Transcri#ed In Vitro >*cleic )cid 'y#ridi&ation )llo$s the Detection of Specific >*cleotide Se.*ences D>) Can Be C*t and Spliced En&y!atically D>) Se.*encing 6ay ,e eal the Bioche!ical )cti ity of a 1ene Prod*ct Transfection and 1enetic Transfor!ation of Cells The Strategies of 1ene + ere4pression/ Do!inant (nterference and 1ene Knoc3o*t.

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1er! "ine Transfor!ation The 1enetic Transfor!ation of Drosophila Atili&es Transposa#le D>) Ele!ents 6a!!als Can Be Transfor!ed #y (nIecting Transgenes Directly into an Egg Pron*cle*s Transgenic 6ice Can Be ,aised fro! Transfor!ed E!#ryonic Ste! Cells D>) (nsertion Can Be Ased for 6*tagenesis and Pro!oter Trapping Transgenic +rganis!s 'a e 6any Ases in Basic and )pplied Science 3 *ethods '5.' The -eneration and *aintenance of *utants 3 *ethods '5.+ "aturation *uta/enesis "creens 3 *ethods '5., !orthern Blottin/ and "outhern Blottin/ 3 *ethods '5.1 &eco47inant D!A Techni?ues '6 / T&A!" &I%TIO!AL O!T&OL

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The Principle of Differential 1ene E4pression E idence for Transcriptional Control D>) Se.*ences Controlling Transcription ,eg*latory D>) Se.*ences )re St*died $ith %*sion 1enes Pro!oters and Enhancers )re ,eg*latory D>) ,egions $ith Different Properties 18.0 Transcription %actors and Their ,ole in De elop!ent 1eneral Transcription %actors Bind to )ll Pro!oters Transcriptional )cti ators and ,epressors )ssociate $ith ,estricted Sets of 1enes and +cc*r +nly in Certain Cells Transcriptional )cti ators 'a e 'ighly Conser ed D>) Binding Do!ains The #icoid Protein )cts as a Transcriptional )cti ator on the hunchback+ 1ene in the Drosophila E!#ryo The )cti ity of Transcription %actors The!sel es 6ay Be ,eg*lated 18.2 Chro!atin Str*ct*re and Transcription 'eterchro!atic Chro!oso!e ,egions )re >ot Transcri#ed P*ffs in Polytene Chro!oso!e )re )cti ely Transcri#ed D>) in Transcri#ed Chro!atin (s Sensiti e to D>ase ( Digestion Transcriptional Control Depends on 'istone )cetylation and Deacetylation 18.8 Transcriptional Control and Cell Deter!ination Co!#inatorial )ction of Transcription %actors E4plains the Step$ise Process of Cell Deter!ination Cell Deter!ination 6ay Be Based on Bista#le Control Circ*it of S$itch 1enes Drosophila 'o!eotic 1enes Sho$ S$itch 1ene Characteristics D>) 6ethylation 6aintains Patterns of 1ene E4pression 3 *ethod '6.' In Situ $y7ridi@ation 16.1 18.2 18.-

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Posttranscriptional 6odifications of Pre<6essenger ,>) Control of De elop!ent #y )lternati e Splicing ) Cascade of )lternati e Splicing Steps Controls Se4 De elop!ent in Drosophila )lternati e Splicing of Calcitonin and >e*ropeptide !,>) (s ,eg*lated #y Bloc3age of the Calcitonin<Specific Splice )cceptor Site 19.6essenger ,>P Transport fro! >*cle*s to Cytoplas! >*clear Pore Co!ple4es )re Controlled 1ates for the Transport of ,>Ps to the Cytoplas! E4peri!ents $ith Cloned cD>)s (ndicate Differential !,>P ,etention 19.0 6essenger ,>) Degradation The 'alf<"ife of 6essenger ,>)s in Cells (s ,eg*lated Selecti ely The Degradation of !,>)s in Cells (s Controlled #y Proteins Binding to Specific ,>) 6otifs 3 *ethod '8.' &i7onuclease %rotection Assay 3 *ethod '8.+ %ulse La7elin/ of *olecules and Their $alfAlife in ells ': / T&A!"LATIO!AL O!T&OL A!D %O"T&A!"LATIO!AL *ODIFI ATIO!"

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1;.0

1;.2

%or!ation of Polyso!es and >ontranslated !,>P Particles 6ost !,>)s )re (!!ediately ,ecr*ited into Polyso!es and Translated So!e !,>)s )re Stored as >ontranslated !,>P Particles 6echanis!s of Translational Control Calci*! (ons and p' 6ay ,eg*late the + erall ,ate of Protein Synthesis at %ertili&ation Phosphorylation of (nitiation %actors and )ssociated Proteins Controls Translation ,eg*latory Proteins or ,>)s L6as3M Critical Se.*ences of Specific !,>)s Polyadenylation and Deadenylation Control the Translation of Specific !,>)s Translational Control in +ocytes/ Eggs/ and E!#ryos Early E!#ryos Ase !,>) Synthesi&ed D*ring +ogenesis Specific !,>)s Shift fro! S*#ri#oso!al !,>P Particles to Polyso!es d*ring +ocyte 6at*ration Translation of So!e !,>)s Depends on Their Cytoplas!ic "ocali&ation Translational Control d*ring Sper!iogenesis Prota!ine !,>) (s Stored in S*#ri#oso!al ,>P Particles #efore Translation 6essenger ,>) 6ay Be Ear!ar3ed for Storage #y (ts 2D AT, or -D A,T Se.*ence Posttranslational Polypeptide 6odifications

Kalthoff / Second Edition Contents

13

Polypeptides )re Directed to Different Cell*lar Destinations Polypeptides 6ay Andergo Se eral Posttranslational 6odifications Protein Degradation (s Differentially Controlled '; / -E!ETI A!D %A&A-E!ETI I!FO&*ATIO!

$A%TE&

19.1 1=.2

1=.-

1=.0

1=.2

1=.8

The Principle of 1enetic and Paragenetic (nfor!ation Self<)sse!#ly Self<)sse!#ly (s Ander Tight 1enetic Control The (nitiation of Self<)sse!#ly (s )ccelerated #y Seed Str*ct*res The Confor!ation of Proteins 6ay Change D*ring Self< )sse!#ly )ided )sse!#ly Bacteriophage )sse!#ly ,e.*ires )ccessory Proteins and +cc*rs in a Strict Se.*ence +rder )ided )sse!#ly (s Co!!on in Pro3aryotic and E*3aryotic Cells Directed )sse!#ly +ne Bacterial Protein Can )sse!#ly into T$o Types of %lagella Prion Proteins +cc*r in >or!al and Pathogenic Confor!ations T*#*lin Di!ers )sse!#le into Different )rrays of 6icrot*#*les Centrioles and Basal Bodies 6*ltiply "ocally and #y Directed )sse!#ly Ciliated Proto&oa (nherit )ccidental Cortical ,earrange!ents 1lo#al Patterning in Ciliates The 1lo#al Pattern in Ciliates (s (nherited D*ring %ission The 1lo#al Cell Pattern (s 6aintained D*ring Encyst!ent 1lo#al Patterning (s (ndependent of "ocal )sse!#ly Paragenetic (nfor!ation in 6eta&oan Cells and +rganis!s += / ELL DIFFE&E!TIATIO!

$A%TE&

20.1

2G.2

2G.2G.0

The Principle of Cell Differentiation Each +rganis! 'as a "i!ited >*!#er of Cell Types The Differentiated State (s 1enerally Sta#le The Sa!e Cell Type 6ay Be %or!ed Thro*gh Different De elop!ental Path$ays Cell Differentiation and Cell Di ision So!e Cells Di ide in the Differentiated States +ther Cell Pop*lations )re ,ene$ed fro! Ste! Cells Ste! Cells 6ay Be Anipotent or Pl*ripotent Ste! Cell De elop!ent in 'ydra The +rgani&ation of 'ydra is ,elati ely Si!ple (nterstitial Cells Contain Pl*ripotent and Anipotent Ste! Cells 1ro$th and Differentiation of Blood Cells

14

Kalthoff / Second Edition Contents

2G.2

2G.8

The Sa!e Ani ersal Ste! Cell %or!s )ll Types of Blood Cells as $ell as Endothelial Cells Progenitor Cell Co!!it!ent 6ay Depend on Sta#le Control Circ*its of 1enes and Transcriptional %actors Blood Cell De elop!ent Depends on Colony<Sti!*lating %actors (CS%s) Erythrocyte De elop!ent Depends on S*ccessi e E4pos*re to Different CS%s The )#*ndance of Blood Cells (s Controlled #y Cell Proliferation and Cell Death 1enetic Control of 6*scle Cell Differentiation 6yogenesis is Controlled #y a %a!ily of 6yogenic #'"' Proteins 6yogenic #'"' Proteins 'a e Partially + erlapping %*nction in Vivo (nd*cti e Signals ,eg*late 6yogenic #'"' 1ene )cti ity 6yogenic #'"' Proteins (nteract $ith Cell Cycle ,eg*lators 6yogenic #'"' Proteins Cooperate $ith 6E%2 %actors in )cti ating 6*scle<Specific Target 1enes Ane4pected Potency of Ste! Cells and Prospects for 6edical Ases +' / %ATTE&! FO&*ATIO! A!D E*B&(O!I FIELD"

$A%TE&

21.1 21.2

21.21.0

21.2

,eg*lation and the %ield Concept Characteristics of Pattern %or!ation Pattern %or!ation Depends Apon Cell*lar (nteractions The ,esponse to Patterning Signals Depends on ) aila#le 1enes The ,esponse to Patterning Signals Depends on De elop!ental 'istory Patterning Signals 'a e a 'igh Degree of 1enerality The Concept of ,ecei ing and (nterpreting Positional 7al*e "i!# ,egeneration and the Polar Coordinate 6odel ,egeneration ,estores the Ele!ents Distal to the C*t S*rface (ntercalary ,egeneration ,estores 6issing Seg!ents Bet$een Anli3e Parts "i!# ,egeneration ,ese!#les E!#ryonic "i!# B*d De elop!ent The Polar Coordinate 6odel (s Based on T$o E!pirical ,*les The Polar Coordinate 6odel E4plains S*pern*!erary "i!# %or!ation fro! 6isaligned ,egenerates 6orphogen 1radients as 6ediators of Positional 7al*e ) 6orphogen 1radient Can Specify a ,ange of Positional 7al*es and Polarity to a %ield Positional 7al*es Specified #y 6orphogen 1radients 6ay Elicit Differential 1ene )cti ities and Cell Beha iors 6orphogen 1radients Confer Si&e (n ariance on E!#ryonic %ields )cti in Can %or! a 6orphogen 1radient in Xenopus E!#ryos (nsect De elop!ent 'as Been 6odel #y 6orphogen 1radients

Kalthoff / Second Edition Contents

15

and #y "ocal (nteractions ++ / -E!ETI A!D *OLE ULA& A!AL("I" OF %ATTE&! FO&*ATIO! I! T$E DROSOPHILA

$A%TE&

E*B&(O 22.1 22.2 22.,e ie$ of Drosophila +ogenesis and E!#ryogenesis Cascade of De elop!ental 1ene ,eg*lation 6aternal 1enes )ffecting the )nteroposterior Body Pattern The )nteroposterior and Dorso entral )4es +riginate %ro! the Sa!e Signal The )nterior 1ro*p 1enerates and )*tono!o*s Signal The Posterior 1ro*p )cts #y Depression 6any Posterior<1ro*p 1enes )re )lso ,e.*ired for 1er! "ine De elop!ent The Ter!inal 1ro*p ,elies on the "ocal )cti ation of a ,eceptor Seg!entation 1enes 1ap 1enes )re Controlled #y 6aternal Prod*cts and #y (nteractions )!ong The!sel es Pair<,*le 1enes )re Controlled #y 1ap 1enes and #y +ther Pair<,*le 1enes Seg!ent Polarity 1enes Define the Bo*ndaries and Polarity of Paraseg!ents 6id$ay Thro*gh E!#ryogenesis/ Paraseg!ental Bo*ndaries )re ,eplaced $ith Seg!ental Bo*ndaries 'o!eotic 1enes 'o!eotic 1enes )re E4pressed ,egionally and Specify Seg!ental Characteristics The 'o!eotic 1enes of Drosophila )re Cl*stered in T$o Chro!oso!al ,egions 'o!eotic 1enes )re Part of a Co!ple4 ,eg*latory >et$or3 The Dorso entral Body Pattern The Co!part!ent 'ypothesis Co!part!ents )re Controlled #y the )cti ities of Specific Selector 1ene )cti ities The Ultrabithorax+ E4pression Do!ain Coincides $ith a Co!part!ent Engrailed+ Controls the )nteroposterior Co!part!ent Bo*ndary Apterous+ Controls the Dorso entral Co!part!ent Bo*ndary )ppendage %or!ation and Patterning Co!part!ent (nteractions across Bo*ndaries +rgani&e Pattern %or!ation $ithin Co!part!ents Decapentaplegic Protein %or!s a 6orphogen 1radient in the 5ing (!aginal Disc Patterning 1enes in +ther (nsects +, / T$E &OLE OF HOX -E!E" I! )E&TEB&ATE DE)ELO%*E!T

22.0

22.2

22.8 22.9

22.;

22.=

$A%TE&

16

Kalthoff / Second Edition Contents

23.1

2-.2

2-.-

2-.0

2-.2

23.6

Strategies for (dentifying Patterning 1enes in 7erte#rates 1enes )re Cloned on the Basis of Their Chro!oso!al 6ap Position Pro!oter Trapping (dentifies Patterning 1enes 7erte#rate 1enes Can Be (solated $ith 6olec*lar Pro#es fro! Drosophila 1enes 'o!eotic 1enes and ox 1enes The 'o!eodo!ain is a Cooperati e D>)<Binding ,egion ox 1enes Can Be Di ided in Paralogy and +rthology 1ro*ps The 'o!eodo!ain is 'ighly Conser ed in E ol*tion The ,ole of ox 1enes in the )nteroposterior Body Pattern The +rder of ox 1enes on the Chro!oso!e (s Colinear $ith Their E4pression in the E!#ryo Bo*ndaries of ox 1enes 6ay Ca*se Transfor!ations To$ards 6ore )nterior %ates + ere4pression of ox 1enes 6ay Ca*se Transfor!ations To$ard 6ore Posterior %ates +nly So!e of the Control Syste!s of ox 1ene )cti ity )re E ol*tionarily Conser ed The Dorso entral Body Pattern ) "o#ster 6ay Be 7ie$ed as an Apside<Do$n ,a##it Dorso entral Patterning (s Controlled #y the Sa!e 1enes in %lies and %rogs Pattern %or!ation and ox 1ene E4pression in "i!# B*ds "i!# %ield (nitiation (s )ffected #y %1% Signaling and ox 1ene E4pression T<#o4 1enes Control the Difference Bet$een 'indli!# and %oreli!# The Pro4i!odistal Pattern (s %or!ed in the Progress Bone Signals %ro! So!ites and "ateral Plate Specify the Dorso entral "i!# B*d )4is ) Bone of Polari&ing )cti ity Deter!ines the )nteroposterior Pattern Sonic 'edgehog Protein 'as Polari&ing )cti ity ox 1ene E4pression 6ediates )nteroposterior "i!# Patterning The Principle of ,eciprocal (nteraction +1 / -E!ETI A!D *OLE ULA& A!AL("I" OF %ATTE&! FO&*ATIO! I! %LA!T"

$A%TE&

20.1

20.2

,eprod*ction and 1ro$th of %lo$ering Plants Spore<%or!ing 1enerations )lternate $ith 1a!ete<%or!ing 1enerations Plant E!#ryos De elop (nside the %lo$er and %r*it 6eriste!s at the Tips of ,oot and Shoot )llo$ Plants to 1ro$ Contin*o*sly 1enetic )nalysis of Pattern %or!ation in Plant E!#ryos Si!ilar 6ethods )re Ased for the 1enetic )nalysis of Plant and )ni!al De elop!ent

Kalthoff / Second Edition Contents

17

20.-

20.0

20.2

Pattern %or!ation in Plant E!#ryos (n ol es 22 to 2G Specific 1ene %*nctions 1ro*ps of 1enes Control Distinct Patterning E ents 1enetic Control of %lo$er De elop!ent %loral (nd*ction 1enes Control the %or!ation of an (nflorescence 6eriste! (dentity 1enes Pro!ote the Transition fro! %loral 6eriste!s to (nflorescence 6eriste!s The ,ole of 'o!eotic 1enes in %lo$er Patterning Arabidopsis 'as 'o!eotic 1enes Three Classes of 'o!eotic 1enes Deter!ine the 6orphological Characters of %o*r %lo$er 5horls Do*#le and Triple 'o!eotic Phenotypes Confir! the 1enetic )BC 6odel 'o!eotic 1enes are Controlled #y ,eg*lator 1enes/ 6*t*al (nteractions/ and %eed#ac3 "oops +ther Plants 'a e Patterning 1enes Si!ilar to Those of Arabidopsis Antirrhinum 'as 1enes Controlling +rgan 7ariations 5ithin the Sa!e 5horl 6olec*lar )nalysis of 'o!eotic Plant 1enes The agamous+ 1ene Encodes a Transcription %actor 1enetic and 6olec*lar St*dies ,e eal +rthologo*s 1enes #et$een Arabidopsis and Antirrhinum The Kno$n Plant 'o!eotic 1enes 'a e a 6)DS Bo4 (nstead of a 'o!eo#o4

$A%TE& +5 / E<%E&I*E!TAL A!D -E!ETI A!AL("I" OF CAENORHABIDITIS ELEGANS DE)ELO%*E!T

22.1

22.2

22.-

>or!al De elop!ent 'er!aphrodites and 6ales %ertili&ation/ Clea age/ and )4is %or!ation %o*nder Cells 1astr*lation/ +rganogenesis/ and 'istogenesis "ar al De elop!ent "ocali&ation and (nd*ction D*ring Early Clea age The %irst Clea age 1enerates Blasto!eres $ith Different Potentials P 1ran*les )re Segregated into 1er! "ine Cells Par 1enes )ffect Cytoplas!ic "ocali&ation Three 6aternal Effect 1enes 1enerate a "ocali&ed )cti ity that Pro!otes E6S (dentity Deter!inant )cti ity for the E6S Blasto!ere Deter!ination of )nterior Pharyngeal 6*scle Cells ,e.*ires 6*ltiple (nd*cti e (nteractions P2 Polari&es E6S to %or! Ane.*al Da*ghter Cells 'eterochronic 1enes 6*tations in the lin!"#+ 1ene are 'eterochronic The lin!"#+ 1ene Encodes a >*clear Protein That %or!s a

18

Kalthoff / Second Edition Contents

22.0

22.2

Te!poral Concentration 1radient The lin!#+ 1ene Encodes S!all ,eg*latory ,>)s $ith )ntisense Co!ple!entarity to lin<10 !,>) Do$n<,eg*lation of lin!"#+ E4pression (s (nitiated #y a De elop!ental C*e Progra!!ed Cell Death Progra!!ed Cell Death in C$ elegans (s Controlled #y a 1enetic Path$ay The Strategy of 1enetic 6osaic )nalysis Sho$s That ced!%+ and ced!#+ )ct Cell<)*tono!o*sly The egl!"/ ced!&/ and ced!# 1ene Prod*cts Control the (nitiation of )poptosis The 1enes ces!"+ and ces!'+ Control the Progra!!ed Death of Specific Cells in the Pharyn4 The Prod*ct of a '*!an 1ene/ bcl!'+/ Pre ents Progra!!ed Cell Death in C$ elegans 7*l a De elop!ent The 7*l al Prec*rsor Cells %or! an E.*i alence 1ro*p The 1onadal )nchor Cell (nd*ces The Pri!ary 7PC %ate ) 'ypoder!al Signal (nhi#its 7*l a %or!ation +6 / "E< DETE&*I!ATIO!

$A%TE&

28.1 28.2 28.-

28.0

28.2

En iro!ental Se4 Deter!ination 1enotypic Se4 Deter!ination Se4 Deter!ination in 6a!!als 6aleness in 6a!!als Depends on the ? Chro!oso!e Dosage Co!pensation in 6a!!als +cc*rs #y N Chro!oso!e (nacti ation The %irst 6orphological Se4 Difference )ppears in the 1onad The Testis<Deter!ining %actor )cts Pri!arily in Prospecti e Sertoli Cells 6apping and Cloning of the Testis<Deter!ining %actor Translocated ? Chro!oso!e %rag!ents Ca*sing Se4 ,e ersal )re Ased to 6ap TD% The S,?/ Sry %*nction (s >ecessary for Testis Deter!ination The 6o*se (r)+ 1ene Can Be S*fficient for Testis Deter!ination The (*++ 1ene Controls Pri!ary Se4 Differentiation Se4 Deter!ination and Se4 Differentiation in Drosophila/ C$ elegans and 6a!!als +ne Pri!ary Signal Controls 6*ltiple )spects of Se4 Differentiation The NE) ,atio (s 6eas*red #y >*!erator and Deno!inator Ele!ents Drosophila and C$ elegans 'a e 6aster ,eg*latory 1enes for Se4 Differentiation Dosage Co!pensation 6echanis!s 7ary 5idely The So!atic Se4*al Differentiation +cc*rs $ith Different Degrees of Cell )*tono!y 1er! "ine Se4 Differentiation (n ol es (nteractions $ith

Kalthoff / Second Edition Contents

19

So!atic 1onadal Cells +8 / $O&*O!AL O!T&OL OF DE)ELO%*E!T

$A%TE&

29.1 29.2

29.-

29.0

29.2

1eneral )spects of 'or!one )ction 'or!onal Control of Se4 Differentiation in 6a!!als The Synthetic Path$ay for 6ale and %e!ale Se4 'or!ones )re (nterconnected The 1enital D*cts De elop fro! Parallel Prec*rsors/ the 5olffian and 6llerian D*cts 6ale and %e!ale E4ternal 1enitalia De elop fro! the Sa!e E!#ryonic Pri!ordia 'or!onal Control of Brain De elop!ent and Beha ior in 7erte#rates )ndrogen and Estrogen ,eceptors )re Distri#*ted Differently in the Brain )ndrogens Ca*se Seasonal and Se4*ally Di!orphic Changes in the Brains of Birds Prenatal E4pos*re to Se4 'or!ones )ffects )d*lt ,eprod*cti e Beha ior and Brain )nato!y in 6a!!als 'or!onal Control of (nsect 6eta!orphosis (nsect 6olting/ P*pation/ and 6eta!orphosis )re Controlled #y 'or!ones P*ffs in Polytene Chro!oso!es ,e eal 1enes ,esponsi e to Ecdysone 6*ltiple Ecdysone ,eceptors 'a e Tiss*e<Specific )cti ities Early ,eg*latory 1enes Di ersify and Coordinate the ,esponses of Target Cells to Ecdysone 'or!onal Control of )!phi#ian 6eta!orphosis The 'or!onal ,esponse in )!phi#ian 6eta!orphosis (s +rgan<Specific )!phi#ian 6eta!orphosis (s Controlled #y Thyroid 'or!one The Prod*ction of Thyroid 'or!one (s Controlled #y the Brain 7ario*s Defects in 6eta!orphosis Ca*se Paedo!orphic De elop!ent in Sala!anders The ,eceptors for Ecdysone and Thyroid 'or!one Share 6any Properties +: / O&-A!I"*I -&OBT$ A!D O! O-E!E"

$A%TE&

2;.1

2;.2

2;.-

6eas*re!ent and 6echanis!s of 1ro$th 1ro$th is Defined as Change in 6ass 1ro$th 6ay Be (so!etric or )llo!etric 1ro$th +cc*rs #y Different 6echanis!s 1ro$th )nalysis #y 'eterospecific Transplantation The 1ro$th Potential of a "i!# (s a Property of the "i!#Ds 6esoder! The +ptic C*p and the "ens of the Eye )dI*st Their 1ro$th ,ates to Each +ther 1ro$th 'or!ones

20

Kalthoff / Second Edition Contents

2;.0

2;.2 2;.8 2;.9

2;.;

1ro$th %actors >er e 1ro$th %actor Pro!otes the 1ro$th and Differentiation of Certain >e*rons +ther 1ro$th %actors )ffect 6*ltiple Target Cells in a 7ariety of 5ays The Effects of a 1ro$th %actor 6ay Depend on the Presence of +ther 1ro$th %actors 6echanical Control of Cell S*r i al and Di ision Cell Cycle Control T*!or<,elated 1enes +ncogenes )re Dereg*lated or 6*tated Proto<oncogenes Proto<oncogenes Encode 1ro$th %actors/ 1ro$th %actor ,eceptors/ Signal Proteins/ Transcription %actors/ and +ther Proteins +ncogenes )rise fro! Proto<+ncogenes Thro*gh 7ario*s 1enetic E ents T*!or S*ppressor 1enes "i!it the %re.*ency of Cell Di isions 1ro$th and Pattern %or!ation Patterning Signal Control Cell Cycling and 1ro$th "ocal Cell (nteractions )ffect Cell Di ision and 1ro$th +rganis!s 6eas*re 1ro$th #y 6ass or Si&e ,ather Than #y Cell >*!#er +; / "E!E" E! E

$A%TE&

2=.1 2=.2

2=.2=.0

2=.2

Statistical Definition of Senescence E ol*tionary Theory of Senescence The 6*tation )cc*!*lation 'ypothesis %oc*ses on the )ge Distri#*tion in >at*ral Pop*lations Senescence Can Be )scri#ed to )ntagonistic Pleiotropy )ccording to the Disposa#le So!a 'ypothesis/ E ery (ndi id*al is the Te!porary Carrier of 'is/'er 1er! "ine 7ario*s Physiological Ca*ses of Senescence Cell*lar Senescence and Telo!erase So!atic 6a!!alian Cells Sho$ a "i!ited Capacity for Proliferation Chro!oso!al Ends )re Protected #y Telo!eres Telo!erase )cti ity Co*nteracts Cell*lar Senescence "oss of Telo!erase )cti ity is a Safeg*ard )gainst Cancer Da!age fro! +4idants and +rganis!ic Senescence +4idati e Phosphorylation 1enerates )ggressi e +4idants as (nter!ediates +4idants Da!age Cell*lar D>)/ "ipids and Proteins S*pero4ide ,adical Sti!*lates Cell Di ision and 1ro$th )ntio4idati e )gents Delay Senescence