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Researchers identify a molecular switch that controls neuronal migration in the developing brain
Date:11/25/2010

St. Jude Children's Research Hospital investigators have identified key components of a signaling pathway that controls the departure of neurons from the brain niche where they form and allows these cells to start migrating to their final destination. Defects in this system affect the architecture of the brain and are associated with epilepsy, mental retardation and perhaps malignant brain tumors.

The findings provide insight into brain development as well as clues about the mechanism at work in the other developing tissues and organ systems, particularly the epithelial tissue that covers body surfaces. The report appears November 25 in the journal Science online at the Science Express website.

"Neurons are born in germinal zones in the brain, and the places they occupy in the mature brain are sometimes quite a distance away. The cells have to physically move to get to that final destination," said David Solecki, Ph.D., an assistant member of the St. Jude Department of Developmental Neurobiology and the paper's senior author. "If the process is compromised, the result is devastating disruption of brain circuitry that specifically targets children."

In this study, investigators identified not only the molecular complexes that work antagonistically to control departure of brain cells from germinal zones, but also the adhesion molecule that functions as the cells' exit ticket. Solecki and his colleagues showed that high levels of Siah E3 ubiquitin ligase block neuronal departure by tagging a critical part of the cell's migration machinery for degradation through a process known as ubiquitination. Siah's target is Pard3A, which is part of the PAR complex.

By manipulating levels of both Siah and Pard3A, researchers showed that only when neuronal production of Siah falls and Pard3A rises will the cells move out of the germinal zone. The change prompts the cells to alter their migratory path and move toward the lo
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Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert  

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