Final
noon Thursday May 5
I will post answers for any remaining questions
emailed to me by noon on Tuesday May 3
Imprinting results from pre-programmed
differences in DNA methylation of
selected genes in the sperm and egg
Imprinted genes
affect fetal growth
Insulin growth factor 2
(Igf2)
growth
Insulin growth factor 2
receptor (Igf2r)
growth
What happens if dad’s
copy of Igf2 is deleted?
Insulin growth factor 2
(Igf2)
growth
Insulin growth factor 2
receptor (Igf2r)
growth
What happens if mom’s
copy of Igf2 isn’t imprinted?
Beckwith-Weidemann syndrome
Insulin growth factor 2
(Igf2)
Insulin growth factor 2
receptor (Igf2r)
overgrowth
growth
What if mom’s copy
of Igf2r is deleted?
Insulin growth factor 2
(Igf2)
overgrowth
Insulin growth factor 2
receptor (Igf2r)
growth
T F A mouse that inherits a mutant maternal
copy of Igf2 exhibits fetal undergrowth.
T F A mouse that inherits a mutant Igf2r gene
from its mother is born 40% smaller than normal.
T F
Maternal imprinting of the human Igf2r
gene prevents fetal overgrowth.
T F
Maternal imprinting of the human Igf2
gene prevents fetal overgrowth.
T F
Mutations in the paternal copy of the
mouse Igf2 gene cause mice to be born 40% smaller
than normal.
Experiment #2
Chromatin transferred from myoblasts
can transform untreated fat cells.
Transformation frequency suggests
only one or few of the genes have this ability
C3H/10T cells = fibroblast cells (make connective
tissue, synthesize the extracellular matrix and
collagen)
If treated with azacytadine, C3H/10T cells can be
induced to form muscle, fat and cartilage cells.
Ultimately a single gene was identifiedmyoD
-whose expression could convert
any other cell type into muscle cells
Getting the terminology down: C. elegans Vulva
Early larval stage
Anchor cell (AC)
Figure 6.27
Gonad
VPCs
AC
Basement membrane
Gonad
P3.p-P8.p are the Vulva
Precursor Cells (VPCs)
Later larval stage
P5.p,P6.p and P7.p
lineages make the vulva
P3.p,P4.p and P8.p
lineages non-vulval
3° 3° 2° 1° 2°
P3.p P4.p P5.p P6.p P7.p
3°
P8.p
The Ras pathway is abnormally activated in many human
tumors
eg: pancreatic cancer, colorectal cancer, lung adenocarcinoma,
gall bladder cancer, bile duct cancer and thyroid cancer
Another representation of the RAS pathway
(VPC cells)
LIN-3 signal
Inductive and lateral signals induce the vulva
gonad
Anchor cell
VPCs
VPCs after
induction
P8
3° 3° 2°
1°
2°
3°
The primary and
secondary cells
form the vulva
A signal from P6.p actives notch (lin-12) in P5.p and P7.p
Figure 6.27
The transmembrane receptor is the Lin-12 protein, a
receptor protein related to Notch
“ Primary cell”
“ Secondary cells”
Both membrane and receptor are membrane bound!
Generation of Different Cell Types From Equivalent Cells in C. elegans:
Initial specification of the Anchor Cell also requires Notch
The signal:
lag-2
(delta)
Figure 6.28
The receptor:
lin-12 (notch)
If anchor cell signaling is disrupted, all
VPCs cells adopt a non-vulva fate
anchor
cell
gonad
3° cell 3° cell
3° cell
3° cell
no vulva
3° cell
3° cell