Transcript C: not sure
你认为如下电影，哪一部最烂？ A. 夜宴 B. 无极 C. 十面埋伏 D. 英雄 小测验 Signal Signal Gene A signal response Gene A signal response GeneA A has has aa gain-of-function loss-of-function (hyperactive) mutation Gene mutation GeneA A is is aa negative positive factor, the mutation should IfIf Gene enhance the the signal signal response response enhance A: Yes. Yes. A: B: No No B: More test The G protein complex plays a critical role in yeast mating response Ga (-): hyper response, always want to mate Ga mating response Gb (-): No mating response Gb mating response Ga(-) & Gb(-): No mating response A: Gb Ga mating response C: not sure B: Ga Gb mating response Different Signaling strategies Asymmetric division A B Born to be different Inductive signaling A B American way Lateral signaling A B Between the brothers Asymmetric division A B Born to be different From Alberts et al. Molecular Biology of Cell Vegetal pole tissue induces animal pole tissue to produce mesodermal tissue. From Alberts et al. Molecular Biology of Cell Discovery of the Spemman organizer Spemann and Mangold Inductive signaling A B RTK/RAS/MPK pathway growth factor P RTK GRB2 Ras GDP SOS GAP Ras GTP -P phosphatases +P -P -P SUR-8 Raf MEK +P MAPK +P Kinases 14-3-3 KSR CNK HSP etc. +P Transcription factors A: This pathway is the same between human and the worms or flies. B: Some but not all genes are the conserved in these organisms. C: This pathway is very different between human and the worms or the flies. About this pathway - Driven by cancer research and developmental genetics - One of the first signaling pathways extensively characterized by biochemists and geneticists - One of the first systems that demonstrated the extensive collaboration between biochemists and geneticists. Broke the boundaries between disciplines. - The discovery of the conservation of this pathway powerfully pushed the use of model organisms GF RTK GRB2 SOS RAS RAF MEK MPK TF A Drosophila compound eye With ~800 ommatidium WT sevenless Brenner & Benzer’s exploratory vision in 1960s Sydney Brenner MRC C. elegans Seymour Benzer Caltech Drosophila The Sevenless story 1960s. Benzer decided to study behavior using Drosophila 1970s Benzer paid most attention to development of eye. 1970 Don Ready isolated the first sevenless mutation 1970s. Ready: all ommatidia have the same structure, but they do not have the same lineage origin 1976. Ready: retina = neurocrystalline. Previously formed ommatidia as templates for further patterning. 1980s. Tomlinson: sequential cycles of local cell-cell interactions 1987: Sevenless was cloned. First RTK in Development. By Hafen and Rubin. Cell; Banejee and Benzer. Cell. Landmark. How do they know it is a receptor or a signal? Sev Undifferentiated cell 1. Mosaic analysis R7 photoreceptor cell About mosaic analysis A genetic mosaic is an organism carrying cells of different genotypes Question: A somatic mutation in our body leads to a mosaic genotype regarding the gene containing the mutation. A: agree. B. disagree. C. not sure. About mosaic analysis Most of the classical geneticists have been doing germ-line mutagenesis. Therefore, all cells in a given animal have the same genotype (non-mosaic). A: agree. B. disagree. C. not sure. Somatic Recombination * * * ** ** * ** Mitotic recombination: generating mosaic in Drosophila No recombination A B a b A B a b A B a b With recombination A B A B A B a b a b a b 1. Rare. Occur in G2 2. Enhanced by x-ray radiation. Sevenless mosaic analysis QuickTime™ and a Photo - JPEG decompressor are needed to see this picture. From Hartwell et al. textbook A: Sev is a signal B: Sev is a receptor C: not sure Why Sev is a receptor? -Mosaic analysis determined that they act in R7 -Structurally similar to receptor tyrosine kinase - The protein is expressed in the R7 membrane Sev receptor ? Undifferentiated cell R7 photoreceptor cell Discovery of the Bride of Sevenless - 1988, BOSS was isolated by Larry Zipurski by the similar method - failure to response to UV. -It has exactly the same Sevenless phenotype Why was it called BOSS? Mosaic analysis of Boss X-ray WWW+ W+ bossbossboss+ boss+ Mitotic cross over Boss acts in A: R7 B: R1 C: R6 D: R8 E: not sure W- bossW- boss- white boss- W+ boss+ W+ boss+ red Boss+ RT fate is induced by RTK activation Boss signal R8 Boss Sev receptor Undifferentiated cell Sev R7 photoreceptor cell R7 differentiation