Identification of developmental control genes and cell behavior

1
Identification of developmental control genes and
cell behavior
THE NEMATODE WORM

• small and transparent
• 1000 somatic cells and 1000-2000 germ cells
• two sexes a hermaphrodite and a male

2

• small genomic size (6 chromosomes) 20x of E.coli
  and 1/30 of human
  
• developmental cycle 3 days
• lineage analysis (behavior of all of the cells
  from the egg to the animal) was done
  
• can follow the movements of individual cells
• random variations do not occur predictable cell
  lineage and cell divisions

3
Induction of vulva
Formation of vulva -the egg laying orifice in a
hermaphrodite The "anchor cell" is responsible fo
r generating a passage way laser ablation experi
ments ablate the anchor cells
instead of forming a vulva,hypodermal cells
are formed
4
The pathway for vulva induction
5
How to identify genes involved in vulva formation
Genetic screening for "vulvaless" or "multivulva
" phenotype
6
How many different genes are invovled?
Complementation analysis
7
Question How to determine whether a given gene
functions upstream or downstream from another
gene? (see Fig 21-42)
8
Tests with double mutants
Loss-of-function reduce or abolish the activity
of the gene Recessive
Gain-of-function increase the activity of the
gene
Usually dominant
9
The pathway for vulva induction
10
Heterochronic Mutations
Set of cells behave in a way that would be
appropriate for normal cells at a different stage
in development a daughter cell behaves li
ke its parents or grandparents
11
Lin 14 Heterochornic mutations
keep the cells in an immature state (nuclear
protein)
12
Programmed Cell Death apoptosis
Cell nucleus become condensed, shrivels and
digested (occurs rapidly, and often unnoticed)
Animals have intrinsic cell death program e.g.,
tadpole tail reabsorption during metamorphosis,
digit formation
13
Apoptosis in C. elegans
C. elegans 131 of 1030 somatic cells die
ced9 ( mammalian protooncogene bcl-2) sits
upstream of ced3 and ced4
Ced9
ced-3 and ced-4 the gene products are required
for the cell death
14

• Ced9 loss-of-function increase cell death

Ced9 gain-of-function increased survival,
reduced cell death
Ced9
Ced4/Ced3