The researchers have therefore identified the mechanism that allows stem cell to produce a neuron directly or indirectly by means of the intermediate progenitor. “In our system, when the stress on the downstream signalling pathway is exacerbated, direct neurogenesis is forced to occur”, he continues. “Perhaps during the course of the development of the cortex, a similar physiological signalling pathway exists, independently of stress. The intensity of this signalling, when it is reduced, allows the stem cells involved in neurogenesis to change from direct to indirect”. 

Bingo!

The following step was to verify whether this signalling pathway was present in the different stages of cortical development. “Bingo! We had hit the Jackpot. This proved to be the case. In addition, we noticed a progressive decrease along the development process. We even managed to disturb the physiological expression of this signalling pathway and therefore change the behaviour of the stem cell at an early stage”.  

This discovery could lead to a means of preventing microcephaly. Fundamental research now needs to give way to practical research on the subject. Collaborative efforts between physicians have been created to try to find out if this signalling pathway is altered in patients affected by microcephaly. Furthermore, fœtal alcohol syndrome (characterised by syndromic microcephaly) will be studied: does alcohol abuse by the mother during pregnancy lead to stress, and consequently, an alteration of the signalling pathway which leads to malformation of the cortex? “That will be the next step. We are just at the start of the process. The beauty of this research is that, by basic, non-oriented research, we have discovered interesting mechanisms for human pathology”.  

It would be too hasty to speak of an imminent remedy for the disease. First, the quality of resolution for brain imaging needs to be improved to allow all the indications of microcephaly to be detected by ultrasound so that early intervention can take place. Thereafter, it is possible to imagine a curative treatment (treatment to reduce the severity of the disease) based on molecules that can block the transduction of stress. But once this chemical “cocktail” is injected into the mother, it must overcome the barrier of the placenta in order to reach the embryo. This is no mean feat. Tests are currently being performed on mice. To be continued…