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Molecular determinants of brain formation

Neurological disorders often stem from malformation of a brain structure - the cerebral cortex. Studying the developmental path of this brain region could shed some light on these disorders.
Molecular determinants of brain formation
Mammalian brain is surrounded on the outside by a folded outer layer of neural tissue known as the cerebral cortex. Genetic conditions in which the cortex is not formed properly have devastating consequences. Despite the importance of this structure, our understanding of its development is limited.

The cerebral cortex is further divided into different layers containing the cell bodies of brain’s neurons. Scientists on the EU-funded MIGPCP (Characterization of the role of Scrib1 and Vangl2 in neuronal migration) project decided to investigate the mechanism behind neuronal polarity and migration.

Using conditional knockout mice combined with advanced cell imaging analysis, the consortium focused on the role of the planar cell polarity (PCP) genes Scrib1 and Vangl2 in regulating neuronal migration and cortical development.

Researchers observed the spatial expression of Scrib1 and Vangl2 during development and monitored their effect on the in vitro migration of neurons. Scrib1 gene is associated with autism spectrum disorders. Analysis of Scrib1 mutants revealed that Scrib1 impairment in the whole embryo generates neural tube defects. The consortium generated mice with conditional deletion of this gene. They discovered that Scrib1 is essential for the formation of the corpus callosum, the structure that joins the two brain hemispheres. Results showed that this was due to the mis-localisation of glial cells involved in axonal guidance.

Taken together, the MIGPCP project provided vital molecular insight into the mechanism of cortical layer formation during development. The role of Scrib1 in the neuronal migration process may extend to the regulation of cell proliferation or fate. Given the implication of the cerebral cortex in various neurological disorders, the generated information may open the way for travelling down previously unexplored molecular paths.

Related information


Brain, neurological disorders, cerebral cortex, Scrib1, Vangl2
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