Putting brakes on brain stem cells stops them running out too soon

15 July 2016

Brain stem cell (in green) dividing (the nucleus is labelled in red by a marker of cell division).

Brain stem cell (in green) dividing (the nucleus is labelled in red by a marker of cell division).

Francis Crick Institute scientists have discovered that a protein called Huwel plays a crucial role in slowing down the proliferation of brain stem cells. This allows the brain to keep producing new nerve cells throughout life instead of running out of steam early on.

The research, which was carried out in mice and is likely to translate to humans, gives insight into ageing-related declines in memory and cognitive ability.

Noelia Urbán and Francois Guillemot of the Crick explained: "Throughout life, the human brain produces new nerve cells that have important roles in memory and the control of stress. But little is known about the properties of the stem cells that produce these new neurons."

The researchers used genetic techniques to make mice that lacked Huwel protein. Huwel's function is to destroy another protein, called Asc11, that stimulates the proliferation of brain stem cells.

Initially brain stem cells in these mice proliferated excessively. But several months later (a long time in the life of a mouse!), the growth of new brain stem cells was severely reduced.

The work shows that keeping brain stem cell divisions at a low level is important to prevent them from running out, and therefore preventing new nerve cells from being produced as a mouse - or human - ages.

Dr Guillemot said: "When the brain ages, it loses the capacity to produce new neurons because of a decrease in the number of dividing stem cells. This reduction of stem cell activity has been shown to contribute to the decline in memory and cognitive performance in older mice, and it is presumably also true in older people.

"Improving our understanding of the mechanisms that control the long-term maintenance of brain stem cells might one day help us find ways to counteract the age-related decline in their activity."

The paper, Return to quiescence of mouse neural stem cells by degradation of a proactivation protein, is published in Science.

  • A protein called Huwel plays a key role in slowing down brain stem cell proliferation, making sure that the stem cells don't run out and can continue to produce new nerve cells in the brain throughout life.
  • The Francis Crick Institute researchers worked with colleagues at the Institut Curie at INSERM in Orsay, France and the Center for Proteomics at Erasmus MC in Rotterdam, The Netherlands.
  • This Crick-funded research received additional support from the Wellcome Trust, the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the Netherlands Organisation for Scientific Research, the Federation of European Biochemical Societies and the Fondation de France.