Transcript Chapter 16- Tetrapod limb development

Chapter 16- Tetrapod limb
development
“It is one thing to differentiate the chondrocytes and
osteocytes that synthesize the cartilage and bone matrices;
it is another thing to produce those cells in a temporalspacial orientation that generates a functional bone.”
“How is it that the fingers form at one end of the limb and
nowhere else?”
“How is it that the little finger forms at one edge of the limb and
nowhere else?”
We will use limb development to examine
the larger question of morphogenesis
Human development
5 weeks
11 weeks
Hands
5 weeks
7 weeks
11weeks
Feet
Morphogenic rules
• These rules appear to be the same in all tetrapods
Example- Grafted mammalian limb bud
will direct formation of chick limbs
• These rules must follow a _______________ coordinate system
Dimension
Proteins families involved
1. ________________ (hip-toe)
2. _________________ (thumb-pinky)
3. _________________ (knuckle-palm)
_______________
_______________
_________
Recall from Chapter 11Hox genes dictate
_______________ axis
development
Fig. 11.36- Hox genes
are organized in a
_______________
that concurs with
_________________
structures
This is referred to
as the
____________
Also recall that ____________ has a profound effect on
development by activating _____gene expression
Recall amphibian
development (Ch. 10)
Fig. 10.41
RA
Retinoic acid activates mammalian ____genes
Lacks all
distal
_______
Wild-type
mouse embryo
RA-treated
mouse embryo
Structure of retinoic acid
(not in textbook)
RA
RA receptor
Hox gene
Retinoic acid bind a _______,
then the complex binds
promoter of a ________
Another unusual observationExperiment- Amputate tadpole tail,
then soak the stump in ___
Result- Several _____ develop
How does a _____develop?
Limb development initiates from __________ of _____________ of
_____________ mesoderm and from ___________
Limb bud
_______
Somatic layer of
___________
mesoderm
Fig. 14.1- mesoderm lineages
What dictates forelimb from hindlimb?
• Transcription factor ____ is expressed in mouse ________
• Transcription factor ____ is expressed in mouse _________
• Loss of one copy of _____ gene in humans
results in __________________
Observations-
Normal
Fig. 16.5
•If Place FGF-soaked bead near
forelimb bud, generate a _____
______
•If Place FGF-soaked bead near
hindlimb bud, generate a
__________________
•If Place FGF-soaked bead
between hindlimb and forelimb
buds, generate a ___________
FGF bead inserted
Thus, FGF _______ to make a limb, but tbx5 and tbx4 instruct ______ of limb
Fig. 16.5E Extra wing
from FGF bead placed
near forelimb bud
Fig. 16.5F -Chimera limb from FGF bead placed
between limb buds-
The apical ectodermal ridge (AER) is a critical structure
Generating the ______________ axis
The _______
____________
(AER) is a
critical
structure
AER is required for:
1) ______________,
2) _______________
axis formation,
3) ______ axes
specification
Forelimb AER experiments
AER removed
Limb devel.
ceases
AER duplicated
Duplicate
wing
AER replaced
with leg
mesoderm
chimera
AER replaced
with other
mesoderm
Limb devel.
ceases
AER replaced
by FGF bead
normal
Fig. 16.8
Generating the _____________________ axis
Hox genes specify two things1. Where the limb _______ (recall chapter 11)
2. Whether a cell will become a ________
(humerus), ________ (Ulna and radius) or
an __________ (metacarpels and digits)
9
10
11
12
13
Fig. 16.1
Scalpula
Humerous
Fig. 16.14
Ulna,
Radius
Digits
Metacarpels
Example- If KO Hoxa-11 and Hoxd–11 in
mouse, no _________________
Example- Humans with defective HOX-13
display ________________
Specifying the anterior-posterior limb axis the proximal-distal axis
What dictates thumb-pinky orientation??
1. A group of cell located near ____________ region of
limb bud- called __________________________ (ZPA)
directs polarity
2. These cells in the ZPA express __________________ (Shh)
Evidence
If place Shh bead in
anterior limb bud…
…then
observe
second set of
__________
Extra set
Normal
3. Sonic hedgehog (Shh) activates __________ genes
Hoxd genes specify
_____________
orientation
Fig. 6.15
Specifying the _____________ limb axis
The surrounding ectoderm signal dorsal-ventral axis
•_____ activates ______expression in mesenchyme
•_____ is required to specify ______cell fate
•Lmx1 mutant humans have loss of
_________, ________________
•May also have “____________”
All three axes are ________________
Ectoderm secretes ____…
..which maintains ____ expression in ___..
..which activates ___ genes in limb bud..
..which specifies _____________ limb axis.