Development of the Tetrapod Limb

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Development of the Tetrapod Limb

• BIOL 370 Developmental Biology
• (Chapter 13 9th Edition Chapter 14 10th edition)
• Lange

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Pattern formation study of the tangible
(statistically), orderly outcomes of
self-organization and the common principles
behind similar patterns in nature. In
developmental biology, pattern formation refers
to the generation of complex organizations of
cell fates in space and time. Pattern formation
is controlled by genes.
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Periodicities of limb pattern formation Stylopod
? humerus femur Zeygopod ? ulna radius /
tibia fibula Autopod ? carpals,
metacarpals, phalanges / tarsals, metatarsals,
phalanges
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Figure 13.1 Skeletal pattern of the chick wing
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Figure 13.2 Prospective forelimb fields of the
salamander
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Figure 13.4 Multilimbed Pacific tree frog (Hyla
regilla), the result of infestation of the
tadpole-stage developing limb buds by trematode
cysts
These cysts drive additional limb development
when they feed on the limb bud leading to
splitting of the bud into multiple growing
regions.
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Figure 13.5 Fgf10 expression and action in the
developing chick limb
Fgf10 fibroblast growth factor 10 proteins
encoded by this gene are of the fibroblast growth
factor (FGF) family. FGF family genes all possess
broad based mitogenic and cell survival actions,
including embryonic development.
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Figure 13.6 Molecular model for initiation of
the limb bud in the chick between 48 and 54 hours
of gestation
Watch the process involving the Fgf10 gene.
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Figure 13.7 Specification of limb type in the
chick by Tbx4 and Tbx5 (Part 1)
Tbx4 T-box 4 gene hind limb
development, Tbx5 T-box 5 gene forelimb
development.
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Figure 13.7 Specification of limb type in the
chick by Tbx4 and Tbx5 (Part 2)
In the study in (B) we see a study in which an
FGF bead is inserted in the area between the
action of Tbx4 and Tbx5 resulting in an
additional limb that is chimeric.
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Figure 13.9 Summary of experiments demonstrating
the effect of the apical ectodermal ridge (AER)
on the underlying mesenchyme
Apical Ectodermal Ridge - a structure that forms
from the ectodermal cells at the distal end of
each limb bud and acts as a major signaling
center to ensure proper development of a limb.
After the limb bud induces AER formation, the AER
and limb mesenchymeincluding the zone of
polarizing activity (ZPA)continue to communicate
with each other to direct further limb development
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Figure 13.10 Fgf8 in the apical ectodermal ridge
Fgf8 fibroblast growth factor 8 important
within AER action
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Figure 13.11 The AER is necessary for wing
development
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Figure 13.12 Control of proximal-distal
specification by the progress zone mesenchyme

1. Transplantation of an early wing bud progress
   zone to a late wing bud zone.
2. Transplant of a late wing bud progress zone to an
   early wing bud zone

Extra radius ulna
No extra development
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Figure 13.15 When a ZPA is grafted to anterior
limb bud mesoderm, duplicated digits emerge as a
mirror image of the normal digits
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Figure 13.16 Sonic hedgehog protein is expressed
in the ZPA
ZPA - Zone of Polarizing Activity an area of
mesenchyme that releases signals instructing the
developing limb bud to form along its
anterior/posterior axis.
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Figure 13.17 Ectopic expression of mouse sonic
hedgehog in the anterior limb causes extra digit
formation
The mutant form in (B) is called the Hx mutation
(hemimelic extratoes).
Shh expression that is ectopic (abnormal) can
result in polydactyl digits in these mice.
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Figure 13.18 Deletion of limb bone elements by
the deletion of paralogous Hox genes
Notice how the differential expression of Hox
prologues may shape overall development, but that
there are still many similarities.
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Examples of human polydactly.
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Figure 13.18 Deletion of limb bone elements by
the deletion of paralogous Hox genes (Part 4)
Human Synpolydactyly - (the term means simply,
many fingers joined together) a result of
homozygosity at the HoxD-13 loci. In people with
this syndrome, there is also often malformations
of the urogenital system, which also expresses
this gene.
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Ernest Hemingways home (now a museum) in Key
West Florida houses descendants of his own pet
polydactyl cats. In cat breeding circles, the
polydactyl cats are sometimes called Hemmingway
cats.
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Figure 13.22 Regulation of digit identity by BMP
concentrations in the interdigital space anterior
to the digit and by Gli3
Gli3 ( producing Zinc finger protein Gli3)
represses dHand and Gremlin, which are involved
in developing digits.
This experiment shows a potential mechanism for
webbing of digits.
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Figure 13.26 Patterns of cell death in leg
primordia of (A) duck and (B) chick embryos
Result is a webbed foot. Result is a
non-webbed foot.
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Figure 13.27 Autopods of chicken feet and duck
feet are shown at similar stages
The expression of Gremlin in the duck (arrows) is
thought to prevent the full apoptotic death of
the webbing in the duck.
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Figure 13.28 Inhibition of cell death by
inhibiting BMPs
Gremlin protein soaked beads placed in the
mesodermal webbing of (B) show persistence of the
webbing.
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Figure 13.29 Possible involvement of BMPs in
stabilizing cartilage and apoptosis
BMP and noggin expression may be the cause of the
cartilage defects showin in (C).
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Figure 13.30 Tiktaalik, a fish with wrists and
fingers, lived in shallow waters 375 million
years ago
Tiktaalik - a monospecific genus of extinct
sarcopterygian (lobe-finned) fish from the late
Devonian period, with many features akin to those
of tetrapods. Originally these were first
discovered in northern Canada on Ellesmere
Island.