Proteins are Important for Brain Development

Researchers have found the two main proteins that aid brain development.

The work may one day correct or prevent genetic conditions tied to smaller-than-normal brains and shed light on the evolution of human head size.

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Neurogenesis is the process through which neurons are created during prenatal development to populate the growing brain.

Li-Huei Tsai, director of the Picower Institute and Picower Professor of Neuroscience, found that two proteins-Cdk5rap2 and pericentrin-work together to regulate neural growth in the developing brain. Loss of function of these proteins results in human disorders such as primary autosomal recessive microcephaly (MCPH) and Majewski osteodysplastic primordial dwarfism, type II (MOPDII), genetic conditions characterized in part by abnormally small head circumference.

An understanding of these rare genetic disorders may offer insight into one of the most striking differences between us and our closest living relatives: brain size and cognitive ability.

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The researchers show that Cdk5rap2 and pericentrin interact with one another to regulate proliferation of neural progenitor cells that give rise to the brain layer called the neocortex. Pericentrin recruits Cdk5rap2 to structures within the neural progenitor cells, and loss of Cdk5rap2 results in decreased cell proliferation.

"Given the link between head circumference, intelligence deficits and psychiatric disorders, these findings have implications for our understanding of how abnormalities in brain development can play a role in a number of diseases," said Tsai, a Howard Hughes Medical Institute investigator and the director of the neurobiology program at the Broad Institute's Stanley Center for Psychiatric Research. In addition to leading to potential treatments for MCPH and MOPDII, the work may also shed light on the increase in brain size during human evolution.