Scientists at the Medical Research Council (MRC) have discovered that a gene called Sox9 plays a critical role in how stem cells behave and is crucial in the development of the central nervous system. These results could potentially help researchers manipulate stem cells in the brain and develop new regenerative treatments for stroke, Alzheimer’s disease or brain tumours.

Human embryos develop their nervous systems very early on, from just after two weeks into a pregnancy. From this stage, until about five weeks, the nervous system is largely made up of so-called neuroepithelial cells, which grow rapidly and lay the foundations for our brains and spinal cord. However, it is only after this stage that the various types of nerves and supporting cells seen in the central nervous system begin to appear. These come from stem cells that have the potential to differentiate into different cell types or create more of themselves.

This study shows for the first time in mice is that the gene Sox9 is required for the neuroepithelial cells to turn into these stem cells, and that it continues to be required throughout development and stem cells in the adult brain to retain their properties, such as the ability to self-renew and differentiate.

The study has also established that a gene known as Sonic Hedgehog (Shh) is needed for Sox9 to work. By inducing Sox9 or Shh in neuroepithelial cells, the team found they could kick-start this process early and convert them into neural stem cells. They also found that if there was a genetic defect in Sox9, it was much harder for the mouse to renew damaged nerve cells later on.

This knowledge will be vital for finding new ways to regenerate damaged nerve cells in neurodegenerative diseases such as Alzheimer’s or in cases where the brain has had a severe trauma such as a stroke. It could also pave the way for treatments for certain kinds of brain tumours caused by out-of-control stem cells.

Dr James Briscoe from the MRC National Institute for Medical Research said:

“With the knowledge that the gene Sox9 plays a central role in the development of our nervous system, we are one step closer to being able to control stem cells in the brain and regenerate different kinds of nerve cells. Being able to correct damaged nerve cells would be a huge leap forward for the millions of people with Alzheimer’s, stem cell-related brain tumours or who have suffered from a stroke.”

Stem cell research offers the potential for new treatments for many diseases that currently have no effective cure. MRC researchers are working hard to integrate such cells in living systems so that they can regain function of cells in the spinal cord and brain among others, transforming the opportunities for cell and tissue-based treatments.

1. Neural stem cells are defined by their ability to renew themselves and their potential turn into several different kinds of other cells.