Scientists identify gene needed for brain, cord connections
Susan McConnell
A team of Stanford researchers has identified a specific gene that is necessary for the development of connections between the brain and the spinal cord.
The findings, published in the Proceedings of the National Academy of Sciences (PNAS) and presented at the annual meeting of the American College of Neuropsychopharmacology in December, could be critical for understanding the development of the human brain and treating spinal cord injuries, said biologist Susan McConnell, the Susan B. Ford Professor and senior author of the study.
"Although much progress has been made in elucidating the mechanisms of neuronal fate determination in the vertebrate spinal cord, little is known about the mechanisms that create specificity in higher brain regions, such as the cerebral cortex," McConnell and Stanford co-authors Bin Chen, a research associate, and Laura Schaevitz, a graduate student, wrote in the Nov. 22, 2005, issue of PNAS.
FezlDuring fetal development, specific genes instruct nerve cells on how and where to develop. The Stanford team examined the plasticity of fetal cells in mice to better understand when cells become specialized (limited in their ability to take on new characteristics) or undifferentiated (able to take on new functions or characteristics).
To learn more about crucial developmental stages in the brain, the team removed the gene for Fezl, a DNA-binding protein, to observe its effect on brain development. Mice were used as the animal model because they serve as a powerful genetic representation of human brain circuitry. The results showed that in developing mice that lack Fezl, normal connections to the spinal cord failed to form. Instead, the brain cells that usually form the corticospinal tract, which connects the brain and spinal cord, made inappropriate connections to other parts of the brain. This finding led the researchers to conclude that Fezl is necessary for proper development of neural connections to the spinal cord.
"Normally, Fezl is required for certain brain cells to grow along the pathway that leads into the spinal cord," McConnell said. "In the mice lacking the gene for Fezl, this pattern of corticospinal tract development was not observed."
Spinal injuriesAlthough these findings have yet to be applied in a clinical setting, McConnell said that the discovery of Fezl's role in neural development might one day prove useful in stem-cell research to stimulate axon growth to the spinal cord in injured adults. Fezl and the gene that controls its production could be essential in understanding how to regenerate connections to the spinal cord that are severed during injury, which results in paralysis, she added.
"The discovery of Fezl is a critical finding in unlocking the intricacies of human brain development and could have important implications in the future treatment of spinal cord injuries," McConnell said. "However, there is still much research to be done in identifying the key target genes in the brain. Fezl is another critical step in piecing together a complete picture of brain and spinal cord development."
The study was supported by the National Institutes of Health.
This story is based on an article published by the American College of Neuropsychopharmacology.