During fetal development, genes "instruct" nerve cells on how and where to develop. Researchers examined the plasticity of fetal cells to better understand at what developmental period cells are specialized (i.e., limited in their ability to take on new characteristics) or undifferentiated (i.e., able to be take on new function or characteristics).
In attempting to uncover key developmental moments in the brain, the team removed or "knocked out" 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 major finding of the study was that in developing mice that lack Fezl, normal connections to the spinal cord failed to form. Instead, the brain cells that usually form the spinal cord made inappropriate connections to other parts of the brain. This result led the researchers to determine 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. In the mice lacking the gene for Fezl, this pattern of spinal cord development was not observed," explained senior study author Susan McConnell, Ph.D., Professor of Biological Sciences at Stanford University. "These findings could have important implications in the future treatment of spinal cord injuries."
Though these findings have yet to be applied in a clinical setting, it is possible that researchers could utilize the findings about Fezl in stem cell research attempting to stimulate neuron growth to the spinal cord in injured adults. This protein 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.
"The discovery of Fezl is a critical finding in unlocking the intricacies of human brain development," noted McConnell. "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."