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

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

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

Most lineages do not consist of single tissue types but 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 lineage C. elegans was used to identify the machinery that regulates programmed 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 BrennerH. Robert HorvitzJohn Sulston

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

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

par-3 mutant wildtype 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 L1

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

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

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

Vulva Formation in C. elegans A 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)

The “bag of worms”

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

Does this remind you of anything we learned earlier?