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BERT tells ERNI it's time to grow a brain

9 January 2008

UCL (University College London) scientists have discovered how two proteins ­called BERT and ERNI interact in embryos to control when different organ systems in the body start to form, deepening our understanding of the development of the brain and nervous system and stem cell behaviour.

The new research, published today in PLOS Biology, solves a part of the puzzle of how vertebrates prioritise the order in which they begin to develop different sets of structures. During development only a few signals instruct cells to form thousands of cell types, so the timing of how cells interpret these signals is critical. An international research team led by Professor Claudio Stern of the UCL Department of Anatomy & Developmental Biology has shown that the first stage of development of the brain and nervous system is, paradoxically, a block on its progression.

The scientists describe a sequence of reactions that take place when vertebrate embryos are only a few hours old that together act as a timing mechanism, temporarily stopping the development of neural cells ­─ cells that go on to form the brain and nervous system. This gives a head-start to other cells in the embryo that will go on to create the body's internal organs and skin and prevents the nervous system from developing prematurely.

Dr Costis Papanayotou of the Stern laboratory discovered a new protein ─ BERT ─ which binds with the protein ERNI (previously discovered by Professor Stern's team) and other proteins to unblock a gene (Sox2) that gives the green light to cells to start forming the brain and nervous system.

Professor Stern said: "Scientists have been looking for a long time for the switches that determine when cells in the embryo take on specific roles. Our work shows that the proteins BERT and ERNI have an antagonistic relationship: BERT is stronger and overrides ERNI's suppression of the Sox2 gene, which has a crucial function in setting up the nervous system." As the Sox2 gene is also needed for stem cells to retain their ability to take on a variety of roles in the body and to renew themselves, this research also advances our knowledge of stem cell behaviour, which could have implications for this growing area of medical research.

Notes for Editors

1. For more information, please contact Professor Claudio Stern on +44 (0)20 7679 3346 or e-mail: c.stern@ucl.ac.uk.

2. Alternatively, please contact Jenny Gimpel in the UCL Media Relations Office on tel: +44 (0)20 7679 9726, mobile +44 (0)7747 565 056, out of hours +44 (0)7917 271 364, or e-mail: j.gimpel@ucl.ac.uk.

3. 'A Mechanism Regulating the Onset of Sox2 Expression in the Embryonic Neural Plate' is published in the journal PLOS Biology on Wednesday 9 January 2008. Journalists can obtain copies of the paper by contacting Natalie Bouaravong at PLOS Biology on e-mail: press@plos.org or tel: +1 415 568 3445.

4.   The study was funded by the Medical Research Council, the National Institute of Mental Health (USA), the Ligue Nationale Contre le Cancer, and the European Union Network of Excellence consortium 'Cells into Organs'.

5.   The study was carried out with the Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Lyon, France; the Ecole Normale Supérieure de Lyon, CNRS/INRA, Lyon, France; and the Wellcome/Cancer Research UK Gurdon Institute for Cancer and Developmental Biology, Cambridge, UK.