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Developmental Biology- Grasping the Formation of Hands
The development of human embryos is highly complex with thousands of signalling
molecules constantly communicating with each other in order to maintain the
signalling pathways necessary for specific embryonic formations
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Different signalling
centres are necessary for the formation of the upper limb’s three spatial axes, which
help the anatomy of the hand to develop
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The formation of this limb bud is initiated by the protein sonic hedgehog (Shh)
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Directly under the AER is another signalling
centre, called the progress zone (PZ)
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Animal model experiments were conducted to determine the importance and function
of the AER in development
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The later
the AER was removed in development, the more distal structures were developed,
therefore providing evidence that the AER is required for continued growth
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Moreover, it was noted
that mutations in FGF8 caused distal structures to be truncated 2
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There are numerous limb bud zones corresponding to different parts of the limb,
notably the mesopod forms the future wrist and autopod forms the future hand
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Homeobox proteins are transcription factors
that are regulated in embryonic development, both spatially and in time
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These transcription factors play a key role in certain limb deformities, i
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hand-footgenital syndrome, a common autosomal dominant disease leading to limb
malformation
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The
ability of both humans and primates to oppose their thumbs, thanks to evolution,
gives the dexterity needed for fine, manipulating movements
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Hand-foot-genital syndrome is debilitating as
it causes impaired dexterity due to shortening and apposition of the thumbs
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This patterning is
caused by another signalling centre called the zone of polarising activity (ZPA)
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A

B

C

Figure 1A – the three axis of the hand and the phalangeal and metacarpal bones of the digits
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Figure 1C – more severe syndactyly with incomplete separation of the bones
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Saunders and Gasseling show that
transplantation of cells from the ZPA into the anterior part of the limb bud cause a
mirror imaging effect of the digits along the anteroposterior axis6
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Later Harfe et al
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This was determined through fate mapping of Shhproducing cells
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Specific signals are required to form the
bones of the digits and also the development of synovial joints
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At the sites where interphalangeal synovial joints should be, the cells de-differentiate to form a noncartilaginous zone called an interzone10
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In the embryo a key developmental stage transpires when the fingers that have just
formed, become fully separated around day 54
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A hand anomaly called syndactyly occurs when apoptosis
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separating the digits fails
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Shou et al
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Studies
have also shown that the AER plays a crucial role in apoptosis, due to it containing
receptors for bone morphogenic protein (BMP), which induces programmed cell
death13
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Foetal screening techniques have been developed and are
able to detect these deformities early in development; however future work should
focus on measures to prevent such deformities
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The apical ectodermal ridge is a timer for generating distal
limb progenitors
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2008;135(8): 1395-405
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Limb Patterning: From Signalling Gradients to
Molecular Oscillations
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2014;426(4): 780-784
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Hoxa-13
and Hoxd-13 play a crucial role in the patterning of the limb autopod
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1996;122(10): 2997-3011
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Hand-Foot-Genital Syndrome
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2006
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Patterning mechanisms controlling digit development
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2008; 35(9): 517-24
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Spatiotemporal distribution of mechanisms
that control outgrowth and anteroposterior polarization of the limb bud in the chick embryo
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1973;2(1): 1-12
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Evidence for an
Expansion-Based Temporal Shh Gradient in Specifying Vertebrate Digit Identities
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2004;118: 517-528
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Genetic Evidence that FGFs have an instructive role in
limb proximal-distal patterning
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2008;453(7193): 401-5
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Deconstructing digit chondrogenesis
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2007;29(8):
725-37
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Synovial joints: from development to homeostasis
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2015;13(1): 41-51
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Failure of Differentiation Part I: Syndactyly
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2009;25(2): 171- 193
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Dev Dyn
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Dev Dyn
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13

Pajni-Underwood S, Wilson CP, Elder C, Mishina Y, Lewandoski M
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BMP
signals control limb bud interdigital programmed cell death by regulating FGF signaling
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2007;134(12): 2359-68
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Patterning mechanisms controlling digit development
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2008; 35(9): 517-24
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Embryology of the Upper Limb
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2009; 34(7): 1340-1350

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