Download C: not sure

你认为如下电影，哪一部最烂？
A. 夜宴
B. 无极
C. 十面埋伏
D. 英雄
小测验
Signal
Signal
Gene A
signal
response
Gene A
signal
response
GeneA
A has
has aa gain-of-function
loss-of-function (hyperactive)
mutation
Gene
mutation
GeneA
A is
is aa negative
positive factor, the mutation should
IfIf Gene
enhance the
the signal
signal response
response
enhance
A: Yes.
Yes.
A:
B: No
No
B:
More test
The G protein complex plays a critical role in yeast mating response
Ga (-): hyper response, always want to mate
Ga
mating response
Gb (-): No mating response
Gb
mating response
Ga(-) & Gb(-): No mating response
A:
Gb
Ga
mating response
C: not sure
B:
Ga
Gb
mating response
Different Signaling strategies
Asymmetric
division
A
B
Born to be
different
Inductive signaling
A
B
American way
Lateral signaling
A
B
Between the brothers
Asymmetric
division
A
B
Born to be
different
From Alberts et al. Molecular Biology of Cell
Vegetal pole tissue induces animal
pole tissue to produce mesodermal
tissue.
From Alberts et al. Molecular Biology of Cell
Discovery of the Spemman organizer
Spemann and Mangold
Inductive signaling
A
B
RTK/RAS/MPK pathway
growth factor
P
RTK
GRB2
Ras GDP
SOS
GAP
Ras
GTP
-P
phosphatases
+P
-P
-P
SUR-8
Raf
MEK
+P
MAPK
+P
Kinases
14-3-3
KSR
CNK
HSP
etc.
+P
Transcription factors
A: This pathway is the same between human and the worms or flies.
B: Some but not all genes are the conserved in these organisms.
C: This pathway is very different between human and the worms or the flies.
About this pathway
- Driven by cancer research and developmental genetics
- One of the first signaling pathways extensively
characterized by biochemists and geneticists
- One of the first systems that demonstrated the
extensive collaboration between biochemists and
geneticists. Broke the boundaries between disciplines.
- The discovery of the conservation of this pathway
powerfully pushed the use of model organisms
GF
RTK
GRB2
SOS
RAS
RAF
MEK
MPK
TF
A Drosophila
compound eye
With ~800
ommatidium
WT
sevenless
Brenner & Benzer’s exploratory vision in 1960s
Sydney Brenner
MRC
C. elegans
Seymour Benzer
Caltech
Drosophila
The Sevenless story
1960s. Benzer decided to study behavior using Drosophila
1970s Benzer paid most attention to development of eye.
1970 Don Ready isolated the first sevenless mutation
1970s. Ready: all ommatidia have the same structure, but
they do not have the same lineage origin
1976. Ready: retina = neurocrystalline. Previously formed
ommatidia as templates for further patterning.
1980s. Tomlinson: sequential cycles of local cell-cell
interactions
1987: Sevenless was cloned. First RTK in Development.
By Hafen and Rubin. Cell; Banejee and Benzer. Cell. Landmark.
How do they know it is a receptor
or a signal?
Sev
Undifferentiated cell
1. Mosaic analysis
R7 photoreceptor cell
About mosaic analysis
A genetic mosaic is an organism carrying
cells of different genotypes
Question:
A somatic mutation in our body leads to a mosaic
genotype regarding the gene containing the mutation.
A: agree. B. disagree. C. not sure.
About mosaic analysis
Most of the classical geneticists have been
doing germ-line mutagenesis. Therefore, all
cells in a given animal have the same
genotype (non-mosaic).
A: agree. B. disagree. C. not sure.
Somatic Recombination
*
*
*
**
**
*
**
Mitotic recombination: generating mosaic in Drosophila
No recombination
A B
a b
A B
a b
A B
a b
With recombination
A B
A B
A B
a b
a b
a b
1. Rare. Occur in G2
2. Enhanced by x-ray radiation.
Sevenless mosaic analysis
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
From Hartwell et al. textbook
A: Sev is a signal
B: Sev is a receptor
C: not sure
Why Sev is a receptor?
-Mosaic analysis determined that they act in R7
-Structurally similar to receptor tyrosine kinase
- The protein is expressed in the R7 membrane
Sev receptor
?
Undifferentiated cell
R7 photoreceptor cell
Discovery of the
Bride of Sevenless
- 1988, BOSS was isolated by Larry Zipurski by the
similar method - failure to response to UV.
-It has exactly the same Sevenless phenotype
Why was it called BOSS?
Mosaic analysis of Boss
X-ray
WWW+
W+
bossbossboss+
boss+
Mitotic cross over
Boss acts in
A: R7
B: R1
C: R6
D: R8
E: not sure
W- bossW- boss-
white
boss-
W+ boss+
W+ boss+
red
Boss+
RT fate is induced by RTK activation
Boss signal
R8
Boss
Sev receptor
Undifferentiated cell
Sev
R7 photoreceptor cell
R7 differentiation