Scientists reveal genes controlling limb development

Brussels, 31 October 2006

Our hands and arms gained their asymmetry by copying the architectural genes which control the layout of the main trunk of our bodies, according to research published in the journal Nature.

As an embryo develops, a set of genes known as 'HOX' genes controls the architecture of the growing body. The HOX genes are ordered along the DNA molecule in the same order as the structures which they code for. In the growing embryo, the HOX genes are activated sequentially along the anterior-posterior axis of the body which runs from the head to the toes, so that all of our organs and bones grow in the right places.

This latest study, which was partly funded under the EU's Sixth Framework Programme (FP6), shows that our limbs have effectively copied this architectural system to produce our asymmetrical arms and hands. The researchers found that in the limb bud, HOX genes are activated sequentially along the anterior-posterior axis which runs from the thumb to the little finger. This results in a peak of HOX activity at the posterior (little finger) side of the limb bud. This in turn results in the production of 'Sonic hedgehog' in the posterior part of the limb bud. Sonic hedgehog is a protein which regulates organ and limb development.

It is this asymmetric production of Sonic hedgehog which gives our limbs their characteristic asymmetry and explains why we have an opposable thumb and four fingers of varying sizes. The researchers looked at mice with mutant HOX genes which caused them to produce Sonic hedgehog at both the anterior and posterior parts of the limb; their fore-arms and front paws were perfectly symmetrical, with two little fingers on either side instead of a thumb on one side and a little finger on the other. Absence of the HOX genes controlling fore-arm development lead to mice with just a bony stump below the elbow.

The researchers note that the process of limb development is very similar to the development of the major body plan, which also relies on this sequential activation of HOX genes along an axis. They suggest that the recruitment of the HOX system in growing limbs provided an effective way for tetrapods to develop highly adapted appendages.

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CORDIS RTD-NEWS/© European Communities, 2006
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