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LIMBS
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The fossil record indicates that tetrapod limbs evolved from the fins of sarcopterygian
fish. Eusthenopteron has the same
basic organization of bones in its fins as tetrapods
had in their limbs with the exception of lacking a wrist, ankle, hand
and foot. There were a number of cartilaginous fin rays
in the general area that would later compose the tetrapod
hands and feet. |
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In tetrapod
embryos, the arm and leg begin their development as paddle-like structures. Chick |
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DEVELOPING LIMB IN PIG EMBRYO | ||||||||||||||
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Limb buds possess three important signaling
centers: the apical ectodermal ridge (AER) which
produces FGFs, the zone of polarizing activity
(ZPA) which produces Shh, and the nonridge
ectoderm. FGFs and Shh
control Hox expression (Sanz-Ezquerro,
2003). In the limb bud, the apical
epidermal ridge induces high rates of cell division in the progress zone. The anterior-posterior differentiation of the
limb is controlled by the zone of polarizing activity (ZPA). Apoptosis occurs between the radius and ulna
and between digits to form separated structures (Manouvrier-Hanu,
1999). The growth factors FGF10,
8, 2 and 4 have important roles in limb development such as the induction
of the AER and ZPA (neither of which form in FGF10 mutants) and in the
initiation and maintenance of SHH signaling. (Manouvrier-Hanu,
1999) SHH is secreted from the posterior region
ZPA (and is repressed anteriorly by aristaless-like4)
and helps to determine the anterior-posterior polarity. IHH functions in cartilage development and mutations
can cause polydactyly (Manouvrier-Hanu,
1999). Three zinc finger proteins
(GLI1-3) are involved in the Hedgehog signaling pathway and are homologs of the segment polarity gene cubitus
interruptus.
Interruptions in this pathway can cause polydactyly
with up to 8 digits. (This is interesting
since the earliest known tetrapods possessed
polydactyl hands and feet with up to eight digits). Shh, FGF4, and HoxD13
function at the anterior margin of the limb bud. Interrupting Formin
regulation of Shh can cause the absence of a
thumb, fusion of 3rd and 4th digits, and radio-ulnar syntosis. Mutations in FGF receptor proteins 2 and 3 can
cause syndactyly of hands and feet; brachdactyly, finger-like thumbs, triphalangeal
thumbs, fusion of ankle and wrist, and tibial
curvature, among other changes (Manouvrier-Hanu,
1999). TBX mutations can cause the absence or duplication
of fifth finger among other changes. The TGFβ family
includes BMPs and cartilage-derived morphogenetic
protein (CDMP). Smad proteins (MAD homolog) mediate these signals affect on
the nucleus. BMPs
are the vertebrate homologs of decapentaplegic
genes (Manouvrier-Hanu, 1999). In all coelomate animals,
HOX clusters are important in providing positional information to cells
along an axis. In tetrapods, HOX clusters not only generate an axis along the
length of the body, in the brain, and in the digestive system, they do
so in the limbs as well. In humans
and other vertebrates, HOXD13 and HOXA13 are important for distal part
of limb. HOXD9 is expressed in a more proximal region
of the limb (Manouvrier-Hanu, 1999). |
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One in about
one thousand human births suffers a limb anomaly.
Limb abornmalities include extra digits,
extra carpals, fused carpals, extra phalanges, and the loss of metacarpals,
proximal and middle phalanges. |
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