Transcript Drosophila powerpoint

I can’t wait
to grow up!
Laugh
now
The fruit fly body plan
is self-assembled in 24 hours
How is the body plan specified?
Egg ---> animal
in 24 hours!
Eric Wieschaus and Christiane Nüsslein-Volhard
used genetics to identify proteins that
set up the embryonic body plan
The molecular genetics of
pattern formation in candy corn
Anterior
Posterior
The wild-type pattern
We collected a series of mutants
affecting the body plan
Wild-type
Posterior
group
Anterior group
Morphogenesis
defects
Gap gene
The wild-type body
is segmented
and each segment
has a unique identity
and thus produces
distinctive structures
Wieschaus and
Nüsslein-Volhard
removed single genes
and looked for effects
on the body plan
bicoid mutants have no head!!
Wildtype larva
bicoid mutant
Gilbert Fig. 9.13
Remember that cleavage starts without cell division in
Drosophila
Nurse cells synthesize macromolecules
and pump them into the oocyte
through the cytoplasmic bridges
oocyte
Molecules synthesized by the nurse cells and
specifically localized in the oocyte determine
the anterior/posterior axis of the embryo
Oocyte
Anterior
determinant
= bicoid mRNA
Posterior
determinant
= nanos mRNA
bicoid protein becomes distributed
in a graded fashion
100
Level of
bicoid
0
Bicoid accumulates in a gradient
Head
Tail
Increasing Bicoid concentration
gradient
of the bicoid
transcription factor turns on
A gradientAof
the bicoid
transcription
factor turns on different genes
different genes
at "thresholds"
different "thresholds"
at different
100
Level of
bicoid
0
Gene A- turned on
only by high level
of bicoid
Gene B- turned on
only by intermediate
level of bicoid
Gene C- turned off by
bicoid and thus only on
where bicoid is absent
Hunchback
These
“bicoid target genes”
are known as
the gap genes
Kruppel
Knirps
Expression pattern
of proteins ecoded
by gap genes
Hunchback
Kruppel
Gap gene mutants are missing
different regions of the body
Wildtype
Krüppel hunchback
knirps
The transcription factors encoded by
gap genes cooperate to create even more
complex patterns of gene expression
Expression domain of
gap gene transcription
factor A
Expression domain of
gap gene transcription
factor B
The expression
patterns of gap
gene transcription
factors A and B
overlap
Some genes require
both gap gene
transcription factors A
and B present to be
turned on
Hunchback
Kruppel
Alberts Chapter 8 title page
So, in summary so far…
Maternal Determinants
Zygotic Gap Genes
Zygotic Pair-rule Genes
Figure 9.8(1) Model of Drosophila Anterior-Posterior
Pattern Formation
Isn’t life wonderful, beautiful and incredible!
Ed Lewis was far ahead of his time
who’s
Wildtype
Antennapedia
mutant
T3 and A1 take on a 2nd thoracic identity
T2
T2
T2
A2
Wildtype
Ubx
mutant
All segments take on a 2nd thoracic identity
Wildtype
T2
T3
A1
T2
T2
T2
A8
T2
Ubx abdA
AbdB triple
mutant
Is Ubx is expressed at the right time and place
to make in T3 different from T2?
Yes! Ubx is expressed in T3 and A1
Figure 9.28
Homeotic Gene Expression in Drosophila
The homeotic genes encode
transcription factors that act as
master regulators of segmental identity
Ultrabithorax is expressed in the
region of the embryo that will
become the 3rd thoracic and 1st
abdominal segments
In these segments, Ultrabithorax
protein acts as a transcription
factor that turns on genes specific
for the 3rd thoracic and 1st
abdominal segments
ON
OFF
T1 specific gene
A1 specific gene
ON
A1 specific gene
OFF
A5 specific gene
Ultrabithorax, abdA, and AbdB
normally repress expression
of the“leg gene” Distalless
in the abdominal segments
Distalless in wild-type
T1 T2 T3
Distalless in triple mutant
abdomen
Lewis hypothesized
that the duplication
and diversification
of homeotic
master regulators
underlies the evolution of
an increasingly complex
body plan
The human body
is also
built up from
reiterated units
with different
identities along
the A/P axis
Mouse homeotic genes also encode
transcription factors that act as
master regulators of segmental identity
Hox 3.1 is expressed in the
region of the embryo that will
become the 12th and 13th ribs
In these segments, Hox 3.1 protein
acts as a transcription factor that
turns on genes specific for the
12th and 13th ribs.
ON
12th rib specific
gene
OFF
4th rib specific
gene
OFF
15th rib specific
gene
ON
13th rib specific
gene
As we’ll see later, mammals also have homeotic genes
expressed at different places along the A/P axis
Peer group pressure: The story of the
epidermal versus neural decision in the fruit fly
They started as one
big happy ectodermal
epithelium
I feel a need to
be a neuroblast
Then one of their number got
some big ideas
and started to migrate inside
You guys stay
here and keep up
the good work
As it left, it sent a message to
its neighbors, telling them to
stick with the epidermal fate
The failure of peer group pressure:
Neurogenic mutants in the fruit fly
Some cells become neuroblasts and
signal their neighbors to remain
epidermis
If signal is missing...
All cells eventually invaginate
and become neuroblasts
Nervous system
Epidermis
Extra nervous
system
No
epidermis
Cells lacking signal or lacking receptor
behave differently
+
+
+
+
+
+
+
+
+
Thanks, I
needed that!
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
mutant
mutant
mutant
+
What? I can't
hear you!
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
mutant
mutant
mutant
If mutant cells
lack signal,
they can be rescued by
wild type neighbors
which make signal.
If mutant cells
lack receptor,
they cannot be rescued
by wild type neighbors
which make signal.
Cells lacking signal or lacking receptor
behave differently
+
+
+
+
+
+
+
+
+
Thanks, I
needed that!
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
mutant
mutant
mutant
+
What? I can't
hear you!
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
mutant
mutant
mutant
If mutant cells
lack signal,
DELTA
mutant cells can be rescued
they can be rescued by
by wild
type neighbors.
wild
type neighbors
which
make signal.
Therefore,
DELTA must be the SIGNAL.
If mutantmutant
cells
NOTCH
cells cannot be rescued
lack receptor,
by wild
neighbors.
they
cannottype
be rescued
by
wild type neighbors
Therefore,
NOTCH must be the
which make signal.
Receptor.