3. Life as a worm-- the nematode C. elegans

5. Hermaphrodites do it by themselves

6. An entire C. elegans hermaphrodite worm consists of exactly 959 cells EVERY SINGLE TIME, allowing one to follow the cell lineage.

7. Here’s how it works

8. Was that too fast? Let’s look a bit more closely

10. Most lineages do not consist of single tissue types but the germline and the gut both arise from single founder cells

11. Most lineages do not consist of single tissue types but the germline and the gut both arise from single founder cells

12. Within this lineage is the secret of embryonic development

13. Even cell death is programmed into the lineage C. elegans was used to identify the machinery that regulates programmed cell death in ALL animals

14. The Nobel Prize in Physiology or Medicine 2002 "for their discoveries concerning ’ genetic regulation of organ development and programmed cell death'" Sidney BrennerH. Robert HorvitzJohn Sulston

15. How can lineage control cell fate? One mechanism is through asymmetric segregation of determinants

16. A determinant within the P granules is asymmetrically segregated into one cell at the 16-cell stage. That cell is the progenitor of the germline! DNAP granules Gilbert 8.33

17. par-3 mutant wildtype In par mutants P granules are found in ALL daughter cells

19. Mutations can alter lineages in many ways

20. Example #1- lin-22 Changes in the pattern of cell division

21. Example #1- lin-22 Changes in the pattern of cell division lin-22 is homologous to the Drosophila pair-rule gene hairy

22. Example #2- lin-14 Changes in the timing of cell division L1 L2 L1

23. Scientists studying regulation of lin-14 were the first to identify functions for microRNAs

24. And the heterochronic regulator lin-28 can be part of the recipe For making “induced pluripotent stem cells”

25. Vulva The nematode also provides a great model for organogenesis: e.g., Building the vulva

26. Vulva Formation in C. elegans A paradigm for organogenesis One inducing cell Three receiving cells 22 cells One complete organ

28. The key players One gonadal anchor cells (AC) 6 vulval precursor cells (VPCs)

29. Cell ablations help define the key players

30. The anchor cell (AC) signals to the vulval precursor cells (VPCs) to adopt vulval fates

31. All cells are created equal (or, the road to fame is paved with dead bodies)

33. The “bag of worms”

37. The vul mutations helped define the RTK-Ras pathway, which is mutationally activated in about half of all human tumors

39. Does this remind you of anything we learned earlier?