Life as a worm-- the nematode C. elegans Hermaphrodites do it by themselves.

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