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Life as a worm-- the nematode C. elegans
Life as a worm-- the nematode C. elegans
Hermaphrodites do it by themselves
An entire C. elegans hermaphrodite worm consists of exactly 959 cells
EVERY SINGLE TIME,allowing one to follow the cell lineage.
Here’s how it works
QuickTime™ and aCinepak decompressor
are needed to see this picture.
Was that too fast?
Let’s look a bit more closely
Most lineages do not consist of single tissue typesbut the germline and the gut
both arise from single founder cells
Most lineages do not consist of single tissue typesbut the germline and the gut
both arise from single founder cells
Within this lineage is the secret of embryonic development
Even cell death is programmed into the lineageC. elegans was used to identify
the machinery that regulatesprogrammed cell death in ALL animals
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
How can lineage control cell fate?
One mechanism is through asymmetric segregation of determinants
A determinantwithin the P granulesis asymmetricallysegregated into one cellat the 16-cell stage.
That cell is theprogenitor of thegermline!
DNA P granules
Gilbert 8.33
par-3 mutantwildtype
In par mutants P granules are found in
ALL daughter cells
Mutations can alter lineages in many ways
Example #1- lin-22 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
Example #2- lin-14 Changes in the timing of cell division
L1
L2
L2L1
L1
L1
L1
Scientists studying regulation of lin-14were the first to identify functions for microRNAs
And the heterochronic regulator lin-28 can be part of the recipeFor making “induced pluripotent stem cells”
Vulva
The nematode also provides a great model for organogenesis:
e.g., Building the vulva
Vulva Formation in C. elegansA paradigm for organogenesis
One inducing cell
Three receiving cells
22 cells
One complete organ
The key players
One gonadal anchor cells (AC)
6 vulval precursor cells (VPCs)
Cell ablations help define the key players
The anchor cell (AC) signals to the vulval precursor cells (VPCs) to adopt vulval fates
All cells are created equal (or, the road to fame is paved with dead bodies)
gonad
anchorcell
3° cell3° cell 3° cell
"Vulvaless" mutants:If anchor cell signaling is disrupted
all cells adopt 3° fate.
3° cell 3° cell3° cell
no vulva.
gonad
anchorcell
3° cell3° cell 3° cell
"Vulvaless" mutants:If anchor cell signaling is disrupted
all cells adopt 3° fate.
3° cell 3° cell3° cell
no vulva.
The “bag of worms”
If inhibitory signal to neighborsis blocked, all 3 central cells
adopt 1° fate
Step 1- anchor cell signal normally reaches central 3 cells
gonad
Multivulval mutantsthe consequences of not saying no.
anchorcell
1°/2° cell3° cell3° cell 3° cell1°/2° cell 1°/2° cell
gonad
anchorcell
1° cell3° cell3° cell 3° cell1° cell 1° cell
Extra vulvas
If inhibitory signal to neighborsis blocked, all 3 central cells
adopt 1° fate
Step 1- anchor cell signal normally reaches central 3 cells
gonad
Multivulval mutantsthe consequences of not saying no.
anchorcell
1°/2° cell3° cell3° cell 3° cell1°/2° cell 1°/2° cell
gonad
anchorcell
1° cell3° cell3° cell 3° cell1° cell 1° cell
Extra vulvas
gonad
It takes two steps to make a vulva
anchorcell
1°/2° cell3° cell3° cell 3° cell
Step 1- anchor cell signal reaches central 3 cells
1°/2° cell 1°/2° cell
gonad
anchorcell
2° cell3° cell3° cell 3° cell
Step 2- Central cell sends inhibitory signal to neighbors
1° cell 2° cell
The vul mutations helped define the RTK-Ras pathway,
which is mutationally activatedin about half of all human tumors
gonad
It takes two steps to make a vulva
anchorcell
1°/2° cell3° cell3° cell 3° cell
Step 1- anchor cell signal reaches central 3 cells
1°/2° cell 1°/2° cell
gonad
anchorcell
2° cell3° cell3° cell 3° cell
Step 2- Central cell sends inhibitory signal to neighbors
1° cell 2° cell
Does this remind you of anything we learned earlier?
The transmembrane receptor of the lateral inhibition signal, the lin-12 protein, isa receptor related to the fruit fly Notch protein
lin-12
Lipid bilayer
Inside
Outside
Notch
