2. 2

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

4. This humble animal:
Revealed how cell lineage controls cell fate
Revealed the proteins in the RTK pathway, one of the “big Five”
Taught us about programmed cell death,
key to neural development and mis-regulated in cancer
Gave us insights that led to the discovery of both RNAi and
microRNAs
5. Helped us understand organogenesis at the single cell level

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

6. Think like a geneticist! If you have a single heterozygous mutant
fly or worm, how many generations
till you have a homozygous mutant animal?

7. Hermaphrodites do it by themselves

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

9. Here’s how it works

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

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

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

14. the secret of embryonic development
Within this lineage is
the secret of embryonic development

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

16. The Nobel Prize in Physiology or Medicine 2002
"for their discoveries concerning ’
genetic regulation of organ development
and programmed cell death'"
Sidney Brenner
H. Robert Horvitz
John Sulston

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

18. segregated into one cell at the 16-cell stage. That cell is the
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!
DNA
P granules
Gilbert 8.33

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

21. Mutations can alter lineages in many ways

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

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

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

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

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

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

28. Vulva Formation in C. elegans A paradigm for organogenesis
One inducing cell
Three receiving cells
22 cells
One complete organ 28

30. The key players One gonadal anchor cells (AC)
6 vulval precursor cells (VPCs) 30

31. Cell ablations help define the key players

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

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

35. The “bag of worms”

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

40. This pathway’s so important in Cancer it got 2 spots on this Table!
Here’s Notch

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

45. Remember me?