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Scientists reveal how fingers form

Specific genes determine how fingers are formed

(swissinfo.ch)

Researchers in Geneva have shed new light on how our fingers and toes develop.

In a five-year study, they have unravelled the mechanisms by which digits grow.

The work should offer new understanding into birth defects. It is estimated that one in every 1,000 babies has malformed digits.

Geneva university's zoology department made headlines in the 1990s when it announced that if a gene responsible for digit growth was absent in mice, the animals also failed to develop any genitals.

Fingers and toes

Scientists have known since the 1980s that so-called Hox genes are arranged in the same order as the body parts they help to produce.

The new study, published in Nature magazine, looks at how this works in fingers and toes.

Ten Hox or "architect" genes are responsible for building up our arms and legs properly.

These genes are not scattered throughout the chromosome like other genes but are lined up in a single cluster on the same small piece of one chromosome.

Centre of excellence

"First you get the genes which make the upper arm, then you get the genes which make the forearm and then you get the genes which make the digits," Professor Denis Duboule told swissinfo.

"So there is a correspondence between the way these genes are organised in these little segments and the ordering of the structure that these genes will build up later on during embryonic development - the arms and the legs.

"This is a very enigmatic correspondence and the work we are reporting this week explains how these two things coincide."

The genetics programme led by Duboule is one of Switzerland's new national centres of competence in research, designed to promote outstanding science.

The investigation was carried out by Marie Kmita and Yann Hérault and will continue for three more years.

Birth defects

One child in 1000 suffers from malformed digits as a result of spontaneous genetic mutation. A common defect is the appearance of an extra digit.

"There are many genetic diseases that affect the development of digits," explained Duboule.

"This work not only contributes to our understanding of the way digits develop and how they are built up during development.

"It also sheds light on the mechanisms that can go wrong and that do not work properly and therefore it of course contributes to our understanding of genetic disease affecting digit form and digit number."

Out on a limb

Hox genes are a special set of genes, which regulate the organisation of the body in a wide range of animals.

The DNA in all genes carries instructions for assembling proteins out of chemical building blocks called amino acids. Proteins made by Hox genes can bind to DNA in a way that turns other genes on and off.

Clustered on chromosomes in a developing embryo's cells, these genes switch on and off in sequence.

A Hox gene that turns off early or late can make a dramatic difference in the formation of the embryo.

In the 1990s, Duboule and his colleagues discovered that the same genes that direct a mammalian embryo to sprout digits also tell male embryos to make a penis.

When the "hox" gene responsible for digit growth was absent, the mice also failed to develop any genitals.

swissinfo, Vincent Landon

Key facts

Switzerland currently has 14 National Centres of Competence in Research (NCCR).
The programme to foster excellence in science was launched in 2001.
Each Centre is managed from a university or renowned research institution.
Some 25 NCCRs will eventually be created.

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