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The fruit fly body plan is self-assembled in 24 hours
How is the body plan specified?
Egg ---> animalin 24 hours!
Eric Wieschaus and Christiane Nüsslein-Volhardused genetics to identify proteins that
set up the embryonic body plan
The molecular genetics of pattern formation in candy corn
The wild-type pattern
Anterior
Posterior
We collected a series of mutants affecting the body plan
Wild-type
Anterior group
Gap gene
Posterior group
Morphogenesisdefects
The wild-type body is segmented
and each segment has a unique identityand thus produces
distinctive structures
Wieschaus and Nüsslein-Volhard
removed single genes and looked for effects
on the body plan
Wildtype larva
bicoid mutant
bicoid mutants have no head!!
Gilbert Fig. 9.13
Remember that cleavage starts without cell division in Drosophila
Nurse cells synthesize macromolecules and pump them into the oocytethrough the cytoplasmic bridges
oocyte
Molecules synthesized by the nurse cells and specifically localized in the oocyte determine
the anterior/posterior axis of the embryo
Posterior determinant
Anterior determinant
Oocyte
= bicoid mRNA = nanos mRNA
bicoid protein becomes distributed in a graded fashion
100
0
Level of bicoid
Increasing Bicoid concentration
Head Tail
Bicoid accumulates in a gradient
A gradient of the bicoid transcription factor turns on different genes
at different "thresholds"
100
0
Level of bicoid
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
A gradient of the bicoid transcription factor turns on different genes at
different "thresholds"
These “bicoid target genes”are known as the gap genes
Hunchback
Kruppel
Knirps
Expression patternof proteins ecoded
by gap genes
Hunchback Kruppel
Gap gene mutants are missing different regions of the body
Wildtype Krüppelhunchback 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
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
Expression domain of gap gene transcription
factor B
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
Antennapediamutant
Wildtype Ubx
mutant
T2
A2
T3 and A1 take on a 2nd thoracic identity
T2
T2
WildtypeUbx abdAAbdB triplemutantT2
T3A1
A8
T2T2T2
T2
All segments take on a 2nd thoracic identity
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
A1 specific gene
A1 specific gene
A5 specific gene
T1 specific gene
OFF
OFFON
ON
Ultrabithorax, abdA, and AbdBnormally repress expression of the“leg gene” Distalless in the abdominal segments
Distalless in wild-type
Distalless in triple mutant
T1 T2 T3 abdomen
Lewis hypothesizedthat the duplicationand diversificationof homeotic master regulatorsunderlies the evolution ofan increasingly complexbody plan
The human body is alsobuilt up fromreiterated unitswith different identities alongthe 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.
12th rib specific gene
13th rib specific gene
4th rib specific gene
15th rib specific gene
OFF
OFFON
ON
As we’ll see later, mammals also have homeotic genesexpressed 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
You guys stay here and keep up
the good work
Then one of their number got some big ideas
and started to migrate inside
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
Nervous system
Epidermis
Extra nervous system
No epidermis
Some cells become neuroblasts and signal their neighbors to remain
epidermis
If signal is missing...
All cells eventually invaginate and become neuroblasts
Notch and Delta encode related transmembrane proteins but Delta lacks
a large intracellular domain
Delta
Lipid bilayer
Inside
Outside
Notch
+
+
+mutant
++
++
++
+mutant
mutant +
++
+
+
+
++
++
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++
Cells lacking signal or lacking receptor behave differently
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.
+
+
+mutant
++
++
++
+mutant
mutant +
++
+
+
+
++
++
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++
Thanks, I needed that!
What? I can't hear you!
+
+
+mutant
++
++
++
+mutant
mutant +
++
+
+
+
++
++
++
++
Cells lacking signal or lacking receptor behave differently
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.
+
+
+mutant
++
++
++
+mutant
mutant +
++
+
+
+
++
++
++
++
Thanks, I needed that!
What? I can't hear you!
DELTA mutant cells can be rescued by wild type neighbors. Therefore, DELTA must be the SIGNAL.
NOTCH mutant cells cannot be rescued by wild type neighbors. Therefore, NOTCH must be the Receptor.
A model for the cellular roles of Notch and Delta
Lipid bilayer
Outside
Inside
Delta = membrane-bound
signal"Don't do it-don't be a
neuroblast!"
Lipid bilayer
Inside
Outside
Neuroblast
Notch= receptor
Signaling pathway leading to epidermal
cell fate