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CORNELL BIOMG 1350 - Lecture 16

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3/22/15&1&1. Be&able&to&name&and&describe&the&major&events&of&embryogenesis:&&fer=liza=on,&cleavage,&gastrula=on,&neurula=on&and&organogenesis.&2. Understand&the&changes&in&cell&behavior&that&are&the&basis&for&developmental&events.&3. Know&the&central&ques=ons&in&developmental&biology:&how&do&cells&become&different;&how&do&cells&come&to&be&different&in&a&reproducible&and&organized&way;&how&do&cells&come&to&form&=ssues&and&organs&and&how&do&similar&sets&of&cells&organize&in&different&ways.&4. Learn&the&language&of&development:&e.g.&morphogenesis,&blastula,&blastomere&etc.&Reading:&&Chapter&22,&Molecular&Biology&of&the&Cell&Pages&1305O1320.&Learning&Goals:&From&Single&Cell&to&Organism&Zebrafish&embryo&&Prelim&2&on&Wednesday&!!Special&Office&hours:&!Friday!March!20&&&1:00O2:15&Joel&&107&S=mson&Sunday!March!22&&&1:00O2:00&Kevin&M&&107&S=mson&Monday!March!23&&&1:00O2:00&Jae&&&107&S=mson&&&2:00O3:00&Dante&&&107&S=mson&Tuesday!March!24&&&1:00&O&2:00&Kevin&H&&&G04&S=mson&*note&different&loca=on*&&&2:00&O&3:00&Lucy&&&107&S=mson&&&3:00&O&4:00&Jen&&&107&S=mson&Last&names&AOD,&go&to&Malo^&228&3/22/15&2&Figure 16-33 Essential Cell Biology (© Garland Science 2010) (e.g.&EGF,&NGF)&RTKs&oeen&signal&through&PI83!kinase&(a&lipid&kinase)&and&Akt&(a&serine&threonine&protein&kinase)&to&prevent&cells&from&dying.&&&Apoptosis!=&programmed&cell&death&&Figure 16-34 Essential Cell Biology (© Garland Science 2010) Akt&kinase&blocks&apoptosis&by&maintaining&the&protein&Bcl2&in&an&ac=vated&state&via&phosphoryla=on&of&Bad.&&Light green: 1) survival signal activates RTK Light green connects to blue: 2) activated RTK recruits and activates PI 3-kinase 3) PI 3-kinase phosphorylates inositol phospholipid (it is connected to the cytosolic side of the plasma membrane) 4) phosphorylated inositol phospholipid attracts proteinsBrown: 5) protein is attracted to phosphorylated inositol phospholipid. Dark Green: 6) Akt is activated by protein kinase 1 and protein kinase 2 Akt is now activated. Arrow: 7) Akt is released from plasma membrane Activated Akt promotes cell survivalBad: - in unphosphorylated state, Bad promotes apoptosis by binding and inhibiting a protein (Bcl2) Apoptosis: form of cell deathBcl2: suppress apoptosis unless in unphosphorylated stateSteps: 1) Bad is phosphorylated by Akt 2) Bad releases Bcl2 3) Bcl2 blocks apoptosis -> promotes cell survival3/22/15&3&Figure 16-35 Essential Cell Biology (© Garland Science 2010) RTK&signaling&through&the&serine/threonine&kinases&Akt!and&Tor&also&regulates&cell&growth.&Tor!–&Target&of&rapamycin,&a&potent&an=Ocancer&drug.&Cell&survival&o Introduce&you&to&the&wonder&of&developmental&biology.&o Introduce&you&to&major&phenomena&and&principles&of&development.&o Provide&examples&of&how&we&study&developmental&biology.&o Sample&what&we&know&(and&don’t&know)&about&mechanisms&of&development.&&o Help&you&decide&if&you&want&to&pursue&further&study&in&developmental&biology.&Upper&level&courses&in&Developmental&Biology:&&BioMG3850&–&Developmental&Biology&&BioMG4450&–&Stem&Cell&Biology&&BioMG4610&–&Development&and&Evolu=on&&BioMG6870&–&Developmental&Gene=cs&&&Goals!of!the!second!part!of!the!course:!Cell growth is caused by Akt activating serine/threonine kinase Tor1) growth factor bind to RTK and activates PI-3-kinase-Akt signaling pathway 2) Akt indirectly activates Tor by phosphorylating and inhibiting a protein that helps to keep Tor shut down 3) Tor stimulates protein synthesis and inhibits protein degradation by phosphorylating key proteins in these processes 4) cell growth occurs3/22/15&4&What!is!included!in!the!study!of!developmental!biology?!Organisms&&&Processes&Reproduc=on&&Animals!Plants&Fungi&Bacteria&Embryology!Juvenile&growth&Metamorphosis/puberty&Adult&growth&Wound&healing&Tissue&homeostasis&Why!study!developmental!biology?!Intellectual&curiosity&–&how&does&it&work?&Medical&relevance&in&vitro&fer=liza=on&cancer&biology&birth&defects&Wound&repair&Poten=al&for&regenera=on&Agricultural&relevance&&maximizing&growth&(yield)&&in&vitro&fer=liza=on&&cloning&of&animals&3/22/15&5&How&do&we&study&development?&Descrip=on&(e.g.&fate&mapping)&Perturba=on&&Experimental&embryology&&Developmental&gene=cs&Apply&tools&of&biochemistry,&cell&and&&molecular&biology&Use&model&organisms&Similar&mechanisms&promote&development&of&all&animals&1)2)3)4)3/22/15&6&As&many&as&50%&of&the&genes&in&worms,&flies,&or&fish&are&also&present&in&humans&and&carry&out&similar&func=ons&Major&events&of&embryonic&development&FerHlizaHon!Cleavage! GastrulaHon! NeurulaHon! Organogenesis!Embryogenesis!Steps of embryonic development: 1) fertilization 2) cleavage 3) gastrulation 4) neurulation 5) organogenesis3/22/15&7&Fer=liza=on&unites&two&haploid&genomes&to&form&the&zygote!!Fer=liza=on&acHvates&the&egg,&ini=a=ng&the&process&of&embryogenesis.&Sea&urchin&egg&undergoing&fer=liza=on&and&ac=va=on&Cleavage&is&a&special&type&of&cell&division&in&which&cells&do&not&grow&Cells&move&from&M&to&S&without&stopping&for&G1&or&G2.&Cleaving&cells&have&a&special&name:&!blastomeres!Frog&embryo&X&X&zygote: diploid cell produced by fusion of a male and a female gamete. fertilized eggcleavage: first cell divisions after fertlization3/22/15&8&At&the&end&of&cleavage&the&embryo&is&called&a&blastula*&*blastodisc&(birds,&fish),&blastocyst&(mouse&and&human),&blastoderm&(insects)&blastomeres!blastula&Sea&urchin&embryo&&The&blastula&then&undergoes&a&drama=c&reorganiza=on&called&gastrulaHon!"It&is&not&birth,&marriage,&or&death,&but&gastrula=on,&which&is&truly&the&most&important&=me&in&your&life."&Lewis&Wolpert&(1986)&3/22/15&9&Gastrula=on&creates&three&germ!layers!ectoderm! endoderm!mesoderm!Gastrula=on&in&a&frog!CrossOsec=on&“morphed”&movie&of&amphibian&gastrula=on&External&view&of&amphibian&gastrula=on&ectoderm: outside layer endoderm: inside layer mesoderm: between the ectoderm and the endodermreorganization3/22/15&10&Ectoderm!Mesoderm!endoderm!Germ!cells!Gastrula=on&creates&three&germ!layers!Soma!Germ!line!ectoderm: - acts as the outer surface - contains epidermal cells of skin - in gastrula3/22/15&11&NeurulaHon&(only&happens&in&vertebrates)&Organogenesis:&&genera=on&of&&organs&Internal&organs&(kidney,&lung,&liver&etc.)&Limbs&(fins,&arms,&legs)&Sensory&organs&(eyes,&ears)&folding of the neural plate when it completely closes the epidermis is on the top. a neural tube forms from the folding of the neural plate3/22/15&12&Major&events&of&embryonic&development&FerHlizaHon!Cleavage!


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CORNELL BIOMG 1350 - Lecture 16

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