Neurons find their place in the developing nervous system with the help of a sticky molecule ( tion. The MDGA1 gene was cloned and ...)

Neurons find their place in the developing nervous system with the help of a sticky molecule

tion.

The MDGA1 gene was cloned and characterized first in rat by O'Leary and two former postdoctoral fellows, E. David Litwack, Ph.D. and Matthias Gesemann, Ph.D. They showed that MDGA1 is a cell adhesion molecule ?a protein enabling cells to attach to other surfaces, something that they must do either to move or sit still and elaborate connections. They also showed that MDGA1 is expressed on subpopulations of migrating neurons throughout the developing nervous system, including layer 2/3 neurons in the neocortex, suggesting that MDGA1 may actually be required for migration.

In the current study, O'Leary and Akihide Takeuchi, M.D., Ph.D., a postdoctoral fellow and the study's first author, tested this hypothesis. They first showed that layer 2/3 neurons make MDGA1 protein as they migrate to their destination. Then, utilizing a cutting-edge molecular technique called RNA interference, the Salk researchers silenced the MDGA1 gene. To do this, they painstakingly performed in utero surgery on embryonic mice ?injecting an interfering RNA molecule into the lateral ventricle, a fluid-filled space next to the neocortex. Application of an electrical current forced the RNA into neural progenitor cells, and it was subsequently inherited by their neuronal progeny that form layer 2/3 and blocked their ability to make MDGA1 protein.

When Takeuchi and O'Leary examined the neocortex a few days later when the mice were born, they discovered that nearly all neurons containing the interfering RNA were stalled in aberrant deeper locations, indicating that loss of MDGA1 protein had stymied their attempt to travel the full distance to layer 2/3 and supporting the original hypothesis. The goal now is to determine how MDGA1 controls neuronal migration and what the long-term consequences are of its loss.

Impaired function of neuronal adhesion molecules has been previously linked to neurological defects in humans. A cell adhesion molecule known as L1 has
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Source:Salk Institute

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( tion. The MDGA1 gene was cloned and ...)Neurons find their place in the developing nervous system with the help of a sticky molecule