Genetic Mechanism could lead to Brain Treatments
British scientists have discovered a genetic mechanism in the development of the nervous system that they say might one day be part of new treatments for stroke, Alzheimer’s disease or brain tumors.
In a study in the journal Nature Neuroscience, the scientists found that a gene, named Sox9, is key to the development of neural stem cells in the human embryo: master cells that develop into brain or spinal tissue. Dr James Briscoe from Britain’s Medical Research Council and team led the study.
- In experiments in mice, they found that by using the Sox9 gene they could kick-start the development of these cells, raising the prospect of one day being able to replace or regenerate damaged brain cells in humans.
From human embryo stage until about 5 weeks; the nervous system which is largely made up of so-called neuroepithelial cells grow rapidly and lay the foundations for brains and spinal cord. It is only after this stage that the various types of nerves and supporting cells that make up the central nervous system begin to appear.
- Human embryos begin to develop their nervous systems just after two weeks from conception, the researchers explained;
- In the study, Sox9 is needed for the neuroepithelial cells to turn into these stem cells. It also continues to be needed to allow stem cells in the adult brain to retain their properties, such as the ability to self-renew and differentiate.
The scientists also found that a gene known as Shh is needed for Sox9 to work.
- The Shh gene encodes a protein that is instrumental in patterning the early embryo. It has been implicated as the key inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites;
- The Shh gene binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes;
- In the absence of SHH, PTC represses the constitutive signaling activity of SMO. In the embryo, it regulates morphogenesis of a variety of tissues and organs, in the adult, it controls stem cell proliferation.
- By artificially adding Sox9 or Shh to neuroepithelial cells in mouse embryos, they found they were able to kick-start the process of converting them into neural stem cells;
- They also found that if there was a genetic defect in Sox9, it was much harder for the mice in their experiments to be able to renew damaged nerve cells later on;
- The technology is controversial, in part because some stem cell lines are derived from embryos or fetuses.
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 tumors or who have suffered from a stroke … although it is likely to be many more years before such treatments for humans are developed. (HWM and K Kelland, Reuters)
