Small brains reveal a gene’s outsize role
Microcephaly is a developmental disorder characterized by significantly reduced brain size and a smaller number of neurons, as well as profound mental retardation. Although several genes have been implicated in this disorder, little is known about its cellular and molecular underpinnings.
In a study published May 13 in The American Journal of Human Genetics, Murat Günel, M.D., Nixdorff-German Professor of Neurosurgery and professor of genetics and neurobiology, and collaborators analyzed DNA from three families affected by an extreme congenital form of this condition resulting in a 90 percent reduction in brain size and abnormal layering of cells in the cerebral cortex.
The team homed in on mutations shared by family members in a gene knownNDE1. In the developing nervous system, NDE1 proteins accumulate at centrosomes—structures critical for cell division—in cells that generate neurons, but the NDE1 mutations found in these families undermine this clustering. These data are evidence for crucial roles of NDE1 and centrosomes in normal production and organization of neurons during development. Also, Günel says, evolutionary changes in NDE1 over 5 million years may underlie the greater size and complexity of human brains relative to those of non-human great apes.