1. Genes Control... Development DNA: Physiology Behavior Infectious Disease Inherited Disease Technology

2. Drosophila melanogaster

3. WHY FLIES… 1) Great Genetics 2) Short life span 3) Small Size 4) Small (sequenced!) Genome

4. Great Genetics!!! Function Protein Biochemical Function Gene Phenotype

6. Red-Eyed and White-Eyed Fruit Flies

8. Eye Color Production in Drosophila

10. yellow

11. ebony

12. vestigial

13. eyeless

14. Curly

15. Drosophila’s Contributions to Genetic Research 1910 First mutation: white eyes (T. H. Morgan) 1913 First genetic map showing genes arranged in a linear order (A. H. Sturtevant) 1916 Proof that genes are located on chromosomes (C. B. Bridges) 1927 X-rays cause mutations and chromosomal rearrangements (H. J. Muller) 1934 First physical mapping of a mutation (T.S. Painter) 1975 First physical mapping of a gene (D. S. Hogness) 1980 First comprehensive analysis of mutants that affect animal development –(C. Nusslein-Volhard, E. Wieschaus, E. Lewis) Nobel Prizes

16. Drosophila Life Cycle

23. Homeotic Mutations: The conversion of one body part into another Haltere to wing transformation

24. Antennae conversion to legs! Dominant, gain of function allele of the Antp gene Developmental Genetics!

25. Cell Proliferation Control During Animal Development and its Relation to Cancer

26. NormalDysplasia Carcinoma in situMalignant carcinoma Cancer develops through gradual changes in cell morphology and properties

27. The Cell Cycle

28. Progress Through The Cell Cycle is Regulated

29. Cyclin Dependent Kinases (cdk) Control Progress Through The Cell Cycle cyclin E/cdk2 cyclin D/cdk4 cyclin A/cdk2 cyclin B/cdk1 cyclin A/cdk1

30. cyclin E/cdk2 cyclin D/cdk4 cyclin A/cdk2 cyclin B/cdk1 cyclin A/cdk1 Gene Expression Regulates Cyclin Dependent Kinase Activity During the Cell Cycle (and vice versa) ….

31. Do Flies Get Cancer? St Johnston, Nat Rev Gen 3:176 (2002) YES! (Sort of…)

32. Genes involved in 74% of human diseases, including cancer, can be found in Drosophila Flies are like little humans with wings… http://superfly.ucsd.edu/homophila/

33. The Cell Cycle What About Development?

34. Drosophila Embryonic Cell Cycles: S G2 M SG1 MS

35. Early Drosophila development occurs in a syncytium

36. Nuclear Division Cycles t = 15 min t = 60 min t = 120 min

37. GFP Labeled Chromosomes* *Courtesy of Rob Saint, University of Adelaide, Australia cover slip gas permeable membrane

38. Mitosis in an Early Fruit Fly Embryo