The development of the nervous system takes place thanks to a complex set of processes which involve numerous proteins, the result of which is the formation of the brain and the spinal cord. The alteration of these processes can lead to severe malformations, which can even be incompatible with life. Two of these essential processes are the extension of the axons and their myelination, carried out by cells called oligodendrocytes and whose appropriate organisation is necessary for the nervous transmission to occur properly. The function that the RhoE protein fulfils in these two processes has been the research matter for the doctoral thesis of Pilar Madrigal, guided at the CEU Cardenal Herrera University by doctors Ignacio Pérez Roger and José Terrado Vicente. The thesis, presented at the CEU UCH with international mention, has been given the highest academic grade on behalf of the evaluating tribunal.
Myelination and axon extension
Using transgenic rats that don’t express the gen that codifies the RhoE protein and with new microscopy techniques, such as the 3DISCO technology which makes it possible to monitor the development of nervous fibres by making the brain transparent, the research of Pilar Madrigal concludes that both myelination as well as axon extension depend on the RhoE protein. As professor José Terrado highlights, “we have observed that the brains of rats which do not express the gen that codifies the RhoE protein show severe deficiencies regarding myelination. Specifically, less of their axons have myelin, and those that do, have their myelin organisation altered. These problems are caused by the fact that, in the absence of RhoE, the development of oligodendrocytes is modified, and they don’t differentiate as well.”
On the other hand, RhoE has also proven to be an essential protein for axon extension in this study as, when it is not produced, some axonal projections suffer severe alterations. Specifically, Terrado explains, “the anterior branch of the anterior commissure, one of the main groups of axons which connects both brain hemispheres, is developed erroneously, without reaching its destination nor producing the connexion between both olfactory bulbs, which is necessary for the olfactory processes to occur appropriately.”
RhoE: the key role of a protein
These results of the “Role of the small GTPase RhoE in myelination and axonal tracts development” thesis, have revealed the importance of RhoE in the development of the central nervous system, in processes as crucial as myelination and the formation of some of the main axonal tracts of the brain.
In this same line of research, professors of the ACDC Group of the CEU UCH already revealed the key role of the RhoE protein in the proliferation, migration and differentiation of neural mother cells. And they also detected that the absence of RhoE causes alterations in the motor system – such as the absence of the common fibular nerve and a delay in the formation of neuromuscular connections – and the cells of the subventricular zone, which proliferate in excess, accumulate and migrate deficiently, which also causes a great reduction of some specific olfactory bulb cell types. These results represent an important contribution to expand knowledge on the creation mechanisms of the central nervous system, and disorders such as demyelinating diseases, including multiple sclerosis.