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A novel function for p27 protein in the control of interneuron migration in the developing cerebral cortex

02 October 2012 Liège, University of

These results by GIGA-Neurosciences researchers (University of Liège, Belgium) increase our understanding of the mechanisms that drive neuronal migration in the cerebral cortex. Disruption of neuronal migration is associated with various neurological disorders characterized by mental retardation, epilepsy,  learning disabilities, or autism.

In a study published in Developmental Cell, the group of Laurent Nguyen, Research Associate of the FRS-FNRS and WELBIO investigator at GIGA-Neurosciences (University of Liège) has discovered a novel function for p27 in the control of interneuron migration in the developing cerebral cortex.

The cerebral cortex is one of the most intricate region of the brain whose formation requires migration and integration of two classes of neurons, the projection neurons and the interneurons. These neurons are born in different places and use distinct migration modes to reach the cortex. While several signalling pathways involving various molecules have already been associated with projection neuron migration, the molecular mechanisms that control interneurons migration remain so far elusive.

In this study, the Nguyen’s group unveiled a novel activity of p27, a protein initialy described for its activity as cell cycle regulator, in dynamic remodelling of the cell skeleton, named cytoskeleton, that underlies tangential migration of interneurons in the cerebral cortex. The first author of the paper, Juliette Godin who is an EMBO postdoctoral fellow in the Nguyen lab, declared : « At the molecular level, p27 acts on two cytoskeletal components, the actin and the microtubules. It promotes nucleokinesis and branching of the growth cone through regulation of actine. In addition, it promotes microtubule polymerisation in extending neurites. Both activities are required for proper tangential migration of interneurons in the cortex».

It is worth noting that microtubules are ubiquitous components of the cytoskeleton that contribute to cell integrity as well as cell migration and cell division. These cellular processes are impaired in various neurological disorders as well as in most cancers. « Our results are of particular significance because they demonstate for the first time that p27 is a microtubule-associated protein that promote their polymerisation», said Laurent Nguyen.

Overall, these results increase our understanding of the mechanisms that drive neuronal migration in the cerebral cortex. Disruption of neuronal migration is associated with various neurological disorders characterized by mental retardation, epilepsy,  learning disabilities, or autism.

http://www.cell.com/developmental-cell/abstract/S1534-5807%2812%2900374-7

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