The Course of Development

2. The Course of Development

3. The Course of Development Time Events

4. The Course of Development Time Events

5. The Course of Development Time Events in time

6. The Course of Development Time Events in time

7. The Course of Development Time Events in time and space . . .

8. The Course of Development Time Events in time and space . . .

9. The Course of Development Time Events in time and space . . .

10. The Course of Development Events in time and space . . . . . . driven by patterned gene expression

11. The Course of Development Understanding Human Development Events in time and space . . . . . . driven by patterned gene expression

12. The Course of Development Understanding Human Development

13. The Course of Development Understanding Human Development

14. The Course of Development Understanding Human Development The fate of cells Intrinsic control? patterned in time and space Extrinsic control?

15. Understanding Human Development Why so difficult? Process 9 mo – 20 yrs Generation 20 yrs Genetic recombination Uncontrolled Genetic manipulation Difficult / Impossible Genome size ~3 billion nucleotides Development Complex How to attack a problem that’s too complex?

16. How to Attack a Complex Problem Probability of getting a full house?

17. How to Attack a Complex Problem Probability of getting a pair?

18. How to Attack a Complex Problem 1 · 3/51 Probability of getting a pair in 2 cards?

19. Simplification can help in understanding complexity

20. Understanding Human Development Why so difficult? Process 9 mo – 20 yrs Generation 20 yrs Genetic recombination Uncontrolled Genetic manipulation Difficult / Impossible Genome size ~3 billion nucleotides Development Complex

21. Understanding Fly Development Still difficult Process 9 mo – 20 yrs ~8 days Generation 20 yrs ~14 days Genetic recombination Uncontrolled Controlled Genetic manipulation Difficult / Impossible Difficult Genome size ~3 billion nucleotides ~170 million nucleotides Development Complex Complex How to simplify further?

22. Understanding Any Development What do we want in a model organism? Process ~8 days Hours Generation ~14 days Hours Genetic recombination Controlled Genetic manipulation Difficult Easy Genome size ~170 million nucleotides Few million nucleotides Development Complex Single phenomenon Does such an organism exist?

23. Bacteria E. coli . . . but no development

24. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

25. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

26. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

27. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation

28. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation Development in time and space

29. heterocysts sucrose Heterocyst differentiation by Anabaena Free-living Nostoc N2 CO2 O2 Matveyev and Elhai (unpublished)

30. heterocysts sucrose NH3 Heterocyst differentiation by Anabaena Free-living Nostoc NH3 N2 O2 CO2 Matveyev and Elhai (unpublished)

31. Time after nitrogen removal 0 h 3 h 6 h 9 h 12 h 18 h Heterocyst differentiation by Anabaena AnabaenaSpatially regulated differentiation N2 fixation

32. Time after nitrogen removal 0 h 3 h 6 h 9 h 12 h 18 h N2 fixation Heterocyst differentiation by Anabaena AnabaenaSpatially regulated differentiation

33. Time after nitrogen removal 0 h 3 h 6 h 9 h 12 h 18 h N2 fixation Heterocyst differentiation by Anabaena AnabaenaSpatially regulated differentiation Development of pattern Mark Hill, University of New South Wales http://anatomy.med.unsw.edu.au/cbl/embryo/Notes/skmus7.htm

34. Fruiting body formation by Myxococcus Herd motility

35. Fruiting body formation by Myxococcus Herd development

36. Fruiting body formation by Myxococcus Extrinsic control over development

37. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation swarmercell

38. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation stalkcell swarmercell

39. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation swarmercell stalkcell

40. Cell cycle of Caulobacter Caulobacter crescentusCell cycle-regulated differentiation Intrinsic control over development

41. Bacterial Development End result... much simpler Anabaena heterocysts Bacillus sporulation Caulobacter cell cycle Myxobacteria fruiting

42. Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation Control of initiation selective gene expression ? How to makethe decision?

43. Bacterial regulation of gene expression Transcriptional factors RNAPol DNA P RNA protein

44. signal Bacterial regulation of gene expression Transcriptional factors DNA binding protein RNAPol No stimulus Stimulus DNA Binding site P No RNA

45. signal Bacterial regulation of gene expression Transcriptional factors DNA binding protein RNAPol No stimulus Stimulus DNA Binding site P No RNA

46. signal RNA protein Bacterial regulation of gene expression Transcriptional factors RNAPol Spo0A No stimulus Stimulus DNA Binding site P

47. K F B A ATP Spo genes P P P P P P K F B A ADP Spo genes spo0A spo0F spo0B kinA Sporulation by Bacillus subtilis Control of initiation selective gene expression Why??? Spores

48. Cell density Control by phosphatases K F B A ATP Spo genes P P P P P P P P K F B A ADP Spo genes kinA spo0A spo0B spo0F Sporulation by Bacillus subtilis Phosphorelay as an integration processing device ? Spores - Cell cycle- DNA damage- Nutrient status

49. Sporulation by Bacillus subtilis Control of initiation of development • Integration of signals through signal transduction • Centers on phosphorylation of master protein • DNA binding protein regulates transcription

50. Fore-spore Mother cell Sporulation by Bacillus subtilis Bacillus subtilisTemporally regulated differentiation Control of timing by selective gene expression Set 0 Set II Set V Set IV Set III