2. 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

3. 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

4. More test The G protein complex plays a critical role in yeast mating response mating response G  (-): hyper response, always want to mate GG G  (-): No mating response mating response GG G  (-) & G  (-): No mating response mating response GG A: GG mating response GG GG B: C: not sure

5. A B Asymmetric division A B Inductive signaling A B Lateral signaling Born to be different American way Between the brothers Different Signaling strategies

6. A B Asymmetric division Born to be different

7. From Alberts et al. Molecular Biology of Cell

8. Vegetal pole tissue induces animal pole tissue to produce mesodermal tissue.

9. Discovery of the Spemman organizer

10. Spemann and Mangold

11. A B Inductive signaling

12. P SOS Ras GRB2 Ras GDP GTP Raf Kinases MEK MAPK +P Transcription factors +P growth factor RTK phosphatases -P SUR-8 14-3-3 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.

15. 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

16. A Drosophila compound eye With ~800 ommatidium

19. WTsevenless

20. Brenner & Benzer ’ s exploratory vision in 1960s Sydney BrennerSeymour Benzer C. elegans Drosophila MRC Caltech

21. 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. The Sevenless story

22. How do they know it is a receptor or a signal? Undifferentiated cellR7 photoreceptor cell Sev 1. Mosaic analysis

23. 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.

24. 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.

25. Somatic Recombination * * * * ** * * * *

26. 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

27. Sevenless mosaic analysis A: Sev is a signal B: Sev is a receptor C: not sure From Hartwell et al. textbook

28. 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 ?

29. 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?

30. 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

31. R8 Undifferentiated cellR7 photoreceptor cell Boss Sev Boss signal Sev receptor R7 differentiation RT fate is induced by RTK activation