Cell Death During Development Cell Proliferation Lloyd A. Greene Cell .

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KEY DEVELOPMENTAL PROCESSESCELL DEATH DURING DEVELOPMENTCELL PROLIFERATIONLLOYD A. GREENECELL MIGRATIONCELL DIFFERENTIATIONJANUARY 31, 2005CELL DEATHAPOPTOTIC DEATHWHAT ARE THE MECHANISMS BY WHICHCELLS DIE DURING DEVELOPMENT?vsPRESENT IN DEVELOPING TISSUESINJURY, TOXINSTHAT GOVERN DEVELOPMENTAL CELL DEATHRESPONSE TO CELLCYTOPLASMIC BLEBBINGCELLULAR & NUCLEAR PYKNOSISSWELLINGTHERE ARE EVOLUTIONARILY CONSERVED MECHANISMNECROTIC DEATHCELL & NUCLEARCHROMATIN CONDENSATIONDNA DEGRADATION BY ENDONUCLEASESDEGRADATION(FORMATION OF DNA LADDER)FORMATION OF MEMBRANE-LIMITEDINTEGRITYAPOPTOTIC BODIESCONTENTSRANDOM DNALOSS OF MEMBRANE& LOSS OF CYTOPLASMICPHAGOCYTOSIS OF APOPTOTIC BODIESELECTRON MICROSCOPIC VIEWS OF NORMAL (a) ANDAPOPTOTIC (b-i) NUCLEITIME LAPSE IMAGES OF A CELL UNDERGOING APOPTOS1

APOPTOTIC BODIES AND NUCLEI ARE CLEARED BYPHAGOCYTOSISCASPASES FAMILY OF EXECUTORS OF APOPTOTIC DEATHEM OF AMACROPHAGEENGULFING ANAPOPTOTIC BODYANDAPOPTOTICNUCLEUSIN THEVENTRICULARWALL OF THEDEVELOPINGMOUSEHEART CYSTEINE PROTEASES THAT CLEAVE AFTER ASPAPOPTOTIC BODY CONSTITUTIVELY PRESENT AS INACTIVE FORMSAPOPTOTIC NUCLEUS ACTIVATED BY CLEAVAGE OR BY INTERACTION WITHCOFACTORS SUCH AS APAF1 AND CYTOCHROME C WHEN ACTIVATED, CLEAVE CELLULARSUBSTRATES,LEADING TO APOPTOTIC DEATHFrom: Abdelwahid et al. Anat. Rec. 256:208 (1999)THE MITOCHONDRIAL PATHWAY OF APOPTOTIC DEATH -THE MITOCHONDRIAL PATHWAY OF APOPTOTIC DEATH -APOPTOTIC STIMULIAPOPTOTIC X BCL2CYTOCHROME CCYTOCHROME CAPAF1APAF1CASPASE ACTIVATIONCASPASE ACTIVATIONTHE RECEPTOR-MEDIATED PATHWAY OF APOPTOTIC DEADEATH PROMOTING RECEPTORS AND LIGANDS FADDLIGANDRECEPTORαTNFαα R1TNFαFAS ligandFASTRAILTRAIL-RαTNFααR1 TNFαpCasp8pCasp8pCasp8Casp8MITOCHONDRIAL PATHWAYpCasp 3Casp8Casp 32

FUNCTIONS OF DEVELOPMENTAL CELL DEATHCELL DEATH AND FORMATION OF THE PROAMNIOCAVITY FROM THE BLASTOCYST 1A. MORPHOGENESIS : SCULPTING/SHAPING STRUCTUCREATION OF CAVITIES AND TUBESFUSION OF TISSUE MASSES (PALATE/NEURAL TUBE)CREATION OF FORM (DIGITS, SEMICIRCULAR CANALSFROM: Coucouvanis and Martin. Cell 83: 279-287 (1995)CELL DEATH AND FORMATION OF THE PROAMNIOCAVITY FROM THE BLASTOCYST 2FROM: Coucouvanis and Martin. Cell 83: 279-287 (1995)FUNCTIONS OF DEVELOPMENTAL CELL DEATHCELL DEATH AND FORMATION OF THE PROAMNIOCAVITY FROM THE BLASTOCYST 3FROM: Coucouvanis and Martin. Cell 83: 279-287 (1995)CELL DEATH AND FORMATION OF DIGITS 1A. MORPHOGENESIS : SCULPTING/SHAPING STRUCTUCREATION OF CAVITIES AND TUBESFUSION OF TISSUE MASSES (PALATE/NEURAL TUBE)CREATION OF FORM (DIGITS)DYING CELLS ARE VISUALIZED BY NILE BLUE STAININGFROM: Chen and Zhao, J. Exp. Zool. 282:691 (1998).3

CELL DEATH AND FORMATION OF DIGITS 2CELL DEATH AND FORMATION OF DIGITS 3FROM: Chen and Zhao, J. Exp. Zool. 282:691 (1998).FROM: Chen and Zhao, J. Exp. Zool. 282:691 (1998).FUNCTIONS OF DEVELOPMENTAL CELL DEATHCELL DEATH AND FORMATION OF THESEMICIRCULAR CANALS 1A. MORPHOGENESIS : SCULPTING/SHAPING STRUCTUCREATION OF CAVITIES AND TUBESFUSION OF TISSUE MASSESCREATION OF FORM (SEMICIRCULAR CANALSFROM: Fekete et al., Development 124: 2451 (1997)CELL DEATH AND FORMATION OF THESEMICIRCULAR CANALS 2CELL DEATH AND FORMATION OF THESEMICIRCULAR CANALS 3A: NORMALB-D: CELL DEATHPARTIALLY BLOCKEDfp fusion plateB.Dying cells are indicatedBy TUNEL stainingFROM: Fekete et al., Development 124: 2451 (1997)FROM: Fekete et al., Development 124: 2451 (1997)4

CELL DEATH AND CARDIAC MORPHOGENESISBLOCKADE OF DEATH IN DEVELOPING HEART OFTLEADS TO DOUBLE OUTLET RIGHT VENTRICLE OTF Outflow TractRA Right AuricleRV Right VentricleLA Left AuricleLV Left VentriclePA Pulmonary ArteryAo AortaLVRVa Apoptotic CardiomyocyteLVPV Pulmonic ValveRVOT Right Ventricular OutflowTractAo AortaPA Pulmonary ArteryOFT Outflow TractFrom: Watanabe et al. Dev. Bio. 240: 274-288 (2001)From: Watanabe et al. Dev. Bio. 240: 274-288 (2001)FUNCTIONS OF DEVELOPMENTAL CELL DEATHCELL DEATH IN THE NEURAL CREST ANDESTABLISHMENT OF CRANIOFACIAL PATTERNB. REGULATION OF CELL MIGRATION ANDPATTERNINGEMIGRATION OF CRANIAL NEURAL CREST & FORMATIOOF SEPARATE MIGRATORY STREAMSFROM: Graham, Koentges and Lumsden, Mol Cell Neurosci 8: 76 (1996)REGULATION OF REPRODUCTIVE TRACT DEVELOPMENT 1FUNCTIONS OF DEVELOPMENTAL CELL DEATHC. DELETION OF UNNEEDED STRUCTURESEMBRYONIC RAT GENITALRIDGES SHOWING:KIDNEY: PRONEPHROS AND MESONEPHROSMÜLLERIAN DUCT (MD)WOLFFIAN DUCT (WDBRAIN: CORTICAL SUBPLATE NEURONSOVARY (Ov)TESTES LSYSTEM: WOLFFIANWOLFFIAN ANDDUCTSDUCTSFROM: Roberts et al., Devel. Bio. 208: 110 (1999)5

REGULATION OF REPRODUCTIVE TRACT DEVELOPMENT NCETESTESANDROGENFEMALEXXDEFAULT PATHWAYREGULATION OF REPRODUCTIVE TRACT DEVELOPMENT 3CELL DEATH DURING MÜLLERIAN DUCT ANDUCTMATURATIONWOLFFIANDUCTREGRESSIONFROM: Roberts et al., Devel. Bio. 208: 110 (1999)D. CULLING: REGULATION OF CELL NUMBERSNERVOUS SYSTEM:MATCHING NEURONS WITH TARGETSMATCHING SCHWANN CELL ANDOLIGODENDROCYTES WITH AXONSNORMAL DEVELOPMENTAL NEURONAL DEATH OCCURS ANDIS REGULATED BY TARGET DERIVED TROPHIC FACTORSNEURON NUMBER IN CHICK IONFUNCTIONS OF DEVELOPMENTAL CELL 446P2P4DEVELOPMENTAL STAGEClarke, Rogers & Cowan J. Comp. Neurol. 167: 125(1976)NEURON NUMBER IN CHICK IONNORMAL DEVELOPMENTAL NEURONAL DEATH OCCURS ANDIS REGULATED BY TARGET DERIVED TROPHIC FACTORSNEURONAL CULLING AS REGULATED BY COMPETITIONFOR TARGET-SUPPLIED TROPHIC D0363840424446P2P4DEVELOPMENTAL STAGEClarke, Rogers & Cowan J. Comp. Neurol. 167: 125(1976)6

NEURONAL CULLING AS REGULATED BY COMPETITIONFOR TARGET-SUPPLIED TROPHIC FACTORNEURONAL CULLING AS REGULATED BY COMPETITIONFOR TARGET-SUPPLIED TROPHIC FACTORFUNCTIONS OF DEVELOPMENTAL CELL DEATHNEURONAL CULLING AS REGULATED BY COMPETITIONFOR TARGET-SUPPLIED TROPHIC FACTOREXTERNALLY SUPPLIED TROPHIC FACTOR BLOCKSDEVELOPMENTAL NEURONAL CULLINGELIMINATION OF ECTOPIC NEURONSE. ELIMINATION OF ECTOPIC, DAMAGED OR UNEECELLSECTOPIC CELLS7

FORMATION OF CLEAR LENS FROM LENS FIBER CELLSFUNCTIONS OF DEVELOPMENTAL CELL DEATHF. PRODUCTION OF STRUCTURES WITHOUTORGANELLESSQUAMOUS EPITHELIUM FROM KERATINOCYTESDEGRADATION OF NUCLEIAND ORGANELLES BYDEATH-LIKE MECHANISMFORMATION OF LENS FROM LENS FIBER CELLSCONSEQUENCES OF FAULTY CELL DEATH MECHANISMEMBRYOGENIC DEFECTS IN A MOUSE LACKING CASPASE EMBRYONIC LETHALITYEXCESSIVE DEATH SPINAL MUSCULAR ATROPHY SEVERE CONGENITAL NEUTROPENIAIMPAIRED DEATH SYNDACTYLY - WEBBED FINGERS/TOES CONGENITAL HEART DEFECTSFrom: Kuida et a Cell:94: 325-337, 19988

a. morphogenesis: sculpting/shaping structu creation of cavities and tubes fusion of tissue masses (palate/neural tube) creation of form (digits, semicircular canals cell death and formation of the proamnio cavity from the blastocyst 1 from: coucouvanis and martin. cell 83: 279-287 (1995) from: coucouvanis and martin. cell 83: 279-287 (1995)