A slowed migration in the absence of miR-22 and miR-124

The doublecortin gene (or DCX) is indispensable for successful projection neuron migration because it controls the multipolar-bipolar transition of the latter. “In the absence of miR-124 and miR-22, this gene is inhibited and the phenotype observed is absolutely characteristic of a problem of multipolar-bipolar conversion”, indicates Laurent Nguyen. “In physiological conditions, a neuron which has become bipolar, and which is in locomotion, remains bipolar. When we invalidate miR-124 and/or miR-22, certain neurons become bipolar but do not remain so. The neurons in locomotion lose this polarity, become multipolar and stop”, he continues. The researchers have observed that the locomotion of these neurons is punctuated by pauses. “Then the neurons re-engage with the radial glia and this corresponds to the reacquisition of a bipolar shape. Most of the neurons finish by arriving in the cortex but they are slowed down”. Why do the projection neurons adopt this very peculiar behavior?  “We think that this is due to the fact that the doublecortin ensures maintenance of the polarity as well as participating in the conversion from multipolar to bipolar”,  explains Laurent Nguyen. In addition, doublecortin is not the only gene involved in multipolar-bipolar transition, many genes can cause defects in this transition when they are mutated. This also explains why, despite the inhibition of doublecortin, the migration of projection neurons took place nonetheless.

This study, the first to demonstrate the importance of certain microRNAs in the control of projection neuron migration, paves the way for new research for an understanding of the regulation of this complex process. In a general way, we observe defects in the expression of microRNAs in different types of illnesses such as cancers or neurological disorders. However, as these biological regulators have only recently been discovered, it remains difficult to determine whether their expression defect is more a cause or a consequence of the diseases in which they have been observed.