The biological controller of gene expression, microRNAs, were discovered in the nineties.  In the context of a study published in Cell Reports, Laurent Nguyen’s team, of GIGA Neurosciences at the University of Liege, has demonstrated for the first time the importance of microRNAs in the control of genes involved in cortical neuron migration.

In order to begin its migration and reach its final position in the cortex, the projection neuron must convert its multipolar shape, in the form of a star to a bipolar shape. This multipolar-bipolar transition of newly-born neurons is a rite of passage, an indispensable stage if the migration is to occur correctly and it generally does. But sometimes this process goes wrong, which can contribute to the onset of neurological disorders characterized by cortical malformation such as lissencephaly. Laurent Nguyen’s team has demonstrated that microRNAs are involved in the fine regulation of genes, which control neuron migration. More precisely, two microRNAs target the gene CoREST which is known to be crucial in projection neuron migration. In the absence of one or the other of these two molecules, the researchers have observed an increase in the expression of the CoREST gene and therefore, ultimately, a deregulation of projection neuron migration.

One of the major evolutionary characteristics of mammals is the extraordinary expansion of the cerebral cortex. In humans, its surface reaches about 2200 cm2, or the equivalent of around four sheets of A4 paper. Composed mainly of projection neurons (80%) and interneurons (20%), this impressive surface fits inside the skull thanks to the formation of cerebral gyri, those sinuous folds bordered by fissures which give the brain the appearance of a plate of macaroni.

It is during embryonic development that the six layers of neurons of the cerebral cortex are formed and become meticulously organized so as to enable humans to have the elaborate, sensory, motor and associated functions they are known to have. “The cerebral cortex develops from the anterior region of the primitive system, the telencephalon”, explains Laurent Nguyen, group leader in the Neurobiology Development Unit at GIGA Neurosciences of the University of Liege.  “Local stem cells give rise to successive waves of neurons that migrate to form the cortex”, continues the associate researcher who works at F.R.S.-FNRS and WELBIO.