The mystery of symmetry is revealed

February 18 2010

 

Some of our organs, such as the liver and the heart, are lateralised. As our bodies develop they mostly display bilateral symmetry across the vertebral column. A new molecular pathway, which plays a role in this symmetry in vertebrates, has recently been discovered by a Franco-American team led by Olivier Pourquié at the Stowers Institute for Medical research, who moved a short while ago to the Institute of Genetics and Molecular and Cellular Biology (CNRS / Inserm / University of Strasbourg). This work was published today, in Nature.

Vertebral symmetry appears early in the course of embryonic development, at the time when somites are formed. Somites are cubic shaped structures from which the vertebrae and the muscles, in particular, are derived. Under the influence of an internal clock, pairs of somites develop, in a periodic manner, starting from the internal cellular layers of the embryo. Retinoic acid, a derivative of vitamin A, appears to play a significant role in controlling the symmetry of the somites. Moreover, it is known that semitogenesis becomes desynchronised in mice which are deficient in retinoic acid.

In a study performed on mouse embryos, the researchers investigated the Rere protein, also known as atrophin 2. They showed that this molecule participates in the activation of the signalling pathway for retinoic acid by forming a complex with two other proteins, Nr2f2 and p300, and a retinoic acid receptor. Mice mutated for the Rere gene show the same retarded somite formation as mice which are deficient in retinoic acid.

Their work also showed that the proteins, Nr2f2 and Rere, control the asymmetry of the signalling pathway for retinoic acid. This asymmetry is required to correct interference with the signals which determine the lateralisation of organs. Hence, this study improves our understanding of how the general symmetry of the body can be reconciled with the lateralisation of some organs.

In man, the anomalies in symmetric development of the somites could be responsible for vertebral symmetry disorders such as scoliosis. A defect in the regulation of functions performed by RERE or Nr2f2 on the retinoic acid signalling pathway may be implicated in the occurrence of these frequent, and sometimes acute, diseases.


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IGBMC
The IGBMC has around 700 personnel and is one of the largest biomedical research units in France, involving the CNRS, Inserm and the University of Strasbourg. The research performed at the IGBMC extends from analysis of protein structures to the study of gene expression mechanisms, whose deregulation accompanies the majority of cancers. Other research topics, such as the biology of embryo development, brain physiology and the genetic basis of human diseases such as mental retardation, are also investigated at the Institute. Many teams at the IGBMC work in close collaboration with the faculty of medicine on various topics ranging from cancer to mental retardation and myopathies.

Reference

“Rere controls retinoic acid signalling and somite bilateral symmetry” Gonçalo C. Vilhais-Neto1,*, Mitsuji Mareuhashi1,2,*,Karen T. Smith1, Mireille Vasseur-Cognet3, Andrew
S.Peterson4, Jerry L. Workman1, O. Pourquié1,2,5,*
1 Stowers Institute for Medical Research
2 Howard Hughes Medical Institute, Kansas City, Missouri 64110, USA
3 Department of Endocrinology, Metabolism, and Cancer, Institut Cochin, Université Paris Descartes, CNRS
(UMR 8104), Inserm U567
4 Genentech, South San Francisco, California 94080, USA.
5 University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
* current address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS (UMR 7104), Inserm
U964, Université de Strasbourg, Illkirch

Nature, February 2010

Research contact

Olivier Pourquié
Director of the IGBMC
Tel: +33 (0)3 88 65 32 16
E-mail: Olivier.Pourquie@igbmc.fr

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