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 Gene A signal response Gene A has a loss-of-function mutation If Gene A is a positive factor, the mutation should enhance the signal response A: Yes. B: No Signal Gene A signal response Gene A has a gain-of-function (hyperactive) mutation If Gene A is a negative factor, the mutation should enhance the signal response A: Yes. B: No
More test The G protein complex plays a critical role in yeast mating response mating response G (-): hyper response, always want to mate GG G (-): No mating response mating response GG G (-) & G (-): No mating response mating response GG A: GG mating response GG GG B: C: not sure
A B Asymmetric division A B Inductive signaling A B Lateral signaling Born to be different American way Between the brothers Different Signaling strategies
A B Asymmetric division Born to be different
From Alberts et al. Molecular Biology of Cell
Vegetal pole tissue induces animal pole tissue to produce mesodermal tissue.
Discovery of the Spemman organizer
Spemann and Mangold
A B Inductive signaling
P SOS Ras GRB2 Ras GDP GTP Raf Kinases MEK MAPK +P Transcription factors +P growth factor RTK phosphatases -P SUR KSR CNK HSP etc. GAP RTK/RAS/MPK pathway 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 RTKRAS MPKMEKGRB2SOSRAFGFTF - 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
A Drosophila compound eye With ~800 ommatidium
WTsevenless
Brenner & Benzer ’ s exploratory vision in 1960s Sydney BrennerSeymour Benzer C. elegans Drosophila MRC Caltech
1960s. Benzer decided to study behavior using Drosophila 1970s Benzer paid most attention to development of eye Don Ready isolated the first sevenless mutation 1970s. Ready: all ommatidia have the same structure, but they do not have the same lineage origin 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. The Sevenless story
How do they know it is a receptor or a signal? Undifferentiated cellR7 photoreceptor cell Sev 1. Mosaic analysis
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 1. Rare. Occur in G2 2. Enhanced by x-ray radiation. A B a b A B a b A B a b No recombination A B a b A B a b A B a b With recombination
Sevenless mosaic analysis A: Sev is a signal B: Sev is a receptor C: not sure From Hartwell et al. textbook
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 Undifferentiated cellR7 photoreceptor cell Sev receptor ?
Discovery of the Bride of Sevenless , 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 W-W- W-W- W+W+ W+W+ boss- boss+ W-W- boss- W-W- white boss- X-ray W+W+ boss+ W+W+ red Boss+ Mitotic cross over Boss acts in A: R7 B: R1 C: R6 D: R8 E: not sure
R8 Undifferentiated cellR7 photoreceptor cell Boss Sev Boss signal Sev receptor R7 differentiation RT fate is induced by RTK activation