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The swing of architect genes

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Posted June 7, 2013

Architect genes are responsible for organizing structures of the body during embryonic development. Some of them, namely the Hox genes, are involved in the formation of forelimbs. They are activated in two successive waves, enabling the formation of the arm, then the hand. A team led by Denis Duboule, a professor at UNIGE and EPFL, Switzerland, and Guillaume Andrey, from the Frontiers in Genetics National Research Center, uncovered the workings of this complex process.

A few days. This is the short period of time during which our body’s construction plan is put in place, during its embryonic life. The appea- rance of limbs and vertebrae is orchestrated by a family of ‘architect’ genes called Hox, each providing precise instructions at a given time. Denis Duboule, a geneticist at the Faculty of Science of the University of Geneva (UNIGE) and at the Swiss Federal Institute of Technology in Lausanne (EPFL), demonstrated that these genes were aligned within our chromosomes according to the order of structures that will emerge: first the components of the shoulder, then the arm, and finally the fingers.

The cluster of Hoxd genes coordinates the operations of limb formation, in particular. These genes are transcribed in two successive waves, allowing the development of the arm, then the hand. “We had already discovered that the genes responsible for the hand were controlled by enhancers, specific DNA sequences located in an adjacent area, at one end of the Hoxd cluster. This regulatory domain takes on a different three-dimensional configuration, according to the degree of activity of the enhancers,” says Professor Duboule.

Two distinct regulatory domains

In order to understand the molecular processes that preside over arm formation, as well as the transition to wrist and hand formation, the researchers used sophisticated techniques of genetic engineering, molecular biology, and murine embryo cell lines. “Curiously, certain Hoxd genes are involved in the origin of both the arm and the hand, while it is their absence of expression that enables wrist formation,” notes Guillaume Andrey, former doctoral student at the Frontiers in Genetics National Research Center and first author of the article.

Read more at: Phys.org

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