Connected Brains: why it is crucial to know how neurons grow
Everyone can appreciate the importance of human connection. These are developed and maintained through communication between an individual and their wider network that keep each of us an integrated part of a wider community. This same can be used to describe the organization of the brain where individual nerve cells (called neurons) establish connections with those closest to them, and also reach out to make connections with neurons in other areas of the brain. These ‘long distance’ connections are called neural pathways. They are essentially the routes through which different parts of the brain communicate. This process of wiring of the brain takes place as the fetus develops during pregnancy. Disruption of this wiring process can lead to changes in specific neural pathways which are seen in disorders like autism. At the other end of life, if specific neural pathways are lost or damaged in old age, this can lead to disorders like Parkinson’s disease. For these reasons a key goal of our research is to identify the factors that control how neurons grow to form neural pathways. This is beneficial in two main ways:
Firstly, it helps us explain why abnormal neural pathways may be found in children that are affected by disorders we may know little about. This is a crucial first step in developing new therapies for these disorders. Secondly, if we understand how neural pathways grow in young brains, we can use this information to develop new therapies to try and re-grow neural pathways that are damaged or lost in old age.
Our recent work funded by Science Foundation Ireland highlights why this kind of research is important. In our recent study published open access in Scientific Reports (https://www.nature.com/articles/s41598-017-08900-3), we report a new mechanism that controls how a specific neural pathway grows during fetal development. In this study we describe a new function for a protein called ZEB2. We discovered that ZEB2 is important for controlling the development of a neural pathway formed by neurons in a region of the brain known as the midbrain. This is an important finding as mutation in the ZEB2 gene leads to a disorder called Mowat-Wilson syndrome in humans. Children affected by this disorder have severe alterations in particular neural pathways in the brain, but why this happens is unclear. Our work helps explain why this occurs by showing that ZEB2 play an important role in controlling how neural pathways affected by Mowat-Wilson syndrome, are formed in the developing brain. Furthermore our findings are important as we have found that ZEB2 controls the formation of the neural pathway that is damaged in Parkinson’s disease in old age. We are now using this information to develop new therapies that target ZEB2 as a new experimental therapy to re-grow this neural pathway in Parkinson’s disease. This is what we mean when we describe our work as being focused on understanding the mechanisms regulating development, degeneration and regeneration.
Schema showing the proposed role for Zeb2 as a cell-autonomous regulator of BMP-Smad1/5 signalling, which promotes neurite growth in mDA neurons.
Author: Gerard O'Keeffe.
This article first appeared on The O'Keeffe Lab blog website as part of their ‘Project updates and Outreach’. See original article below:
https://www.okeeffelab.com/single-post/2017/08/11/Connected-Brains-why-it-is-crucial-to-know-how-neurons-grow