PARIS, August 30 (Benin News) –
Research conducted at the Neuroscience Institute, a joint center of the Spanish National Research Council (CSIC) and Miguel Hernández University, has identified several dozen new regulators involved in guiding axons to neurons to which they must connect, which could be decisive for the development of new therapies for different neurological disorders.
This process is essential in the formation of neural circuits or networks during the development of the nervous system. This work, published in the journal “Advanced Science”, is therefore essential for understanding a process whose alterations can generate neurological disorders and congenital anomalies throughout life.
For the development and functioning of the adult brain, it is essential that the axons of the different types of neurons that make up the nervous system grow and move to places where they will establish synapses with other neurons.
Until now, most of the molecules known to be involved in this process have been signaling proteins that tell axons where they can and cannot move in the developing brain, or when they should be on their way. connect to other neurons.
However, virtually no transcription factors directly involved in the regulation of these signaling molecules that mark the path of axons to their final destination had been identified.
Today, the work of the IN (CSIC-UMH), led by Eloísa Herrera, in collaboration with Ángel Barco, has made it possible to expand the number of regulatory molecules involved in this process by analyzing two subpopulations of retinal cells , called ganglion cells.
These cells, although having equivalent functions in the processing of visual information, differ in the path that their axons follow in their journey to cerebral structures such as the thalamus or the superior colliculus. Thanks to these different paths, the brain can process the images received from each eye and generate a 3D vision.
THE JOURNEY OF THE AXON
Retinal ganglion cells project their axons to two different routes: to the cerebral hemisphere on the same side of the eye from which they originate (ipsilateral ganglion cells), or to the opposite hemisphere (contralateral ganglion cells); in this case, they pass through an X-shaped structure called the optic chiasm, which serves as a crossroads for visual axons.
The axons of neurons located in the area of the retina closest to the nose cross the midline through the optic chiasm, projecting to the opposite hemisphere, while the rest of the axons avoid the midline at the level of the optic chiasm to project to the same side of the brain from which they originate. Among the novel genes identified in this study, gamma-synuclein stands out as an essential element for inducing midline crossing.
“This binary decision of visual axons whether or not to cross the midline at the optic chiasm is essential for perceiving the world in 3D and represents an excellent paradigm to study the mechanisms that allow the connection of visual neurons with other distant neurons in the brain during late embryonic development,” says Herrera.
To find new regulatory mechanisms involved in defining the axonal trajectory, they performed a multi-omics analysis comparing gene expression profiles (the transcriptome) and chromatin occupancy in retinal neurons projecting to ipsilateral and contralateral cerebral hemispheres.
Although many proteins that regulate axon guidance have been identified over the past three decades, the epigenetic and transcriptional mechanisms that control their expression have remained poorly understood. “Our results demonstrate that the newly identified regulators of axon guidance operate in different contexts and open new avenues of research,” says the researcher.
MULTI-OMICS ANALYSIS
Multiomics analysis of the two subpopulations of retinal neurons used in this research, which differ only in the trajectory followed by their axons, has uncovered new genes encoding proteins that were not previously involved in guidance. axons.
The identification of new transcription factors involved in this process is therefore of interest, because it is these proteins that control the expression of other genes by binding to specific DNA sequences and determining where and when they must be activated. or suppressed.
“In summary, our analyzes have identified dozens of new genes potentially involved in axonal pathway selection. These results open the door to innovative therapeutic approaches aimed at restoring damaged neural circuits,” concludes Herrera.