The Complexity of Semaphorin and Plexin Signalling in the Healthy and Diseased Brain

During development, the brain develops from a few cells to a highly connected and complex organ containing ±170 billion communication-cells (neurons) and as many or more supporting-cells. Neurons connect to other neurons via specific protrusions: axons. These axons are constructed with great care during development and act as communication routes in the brain. Specific so-called axon guidance protein families, such as Semaphorins and Plexins, ensure a correct development of these communication routes. In this thesis, Semaphorin-Plexin signalling interactions are examined using a large variety of techniques. One novel finding is that we identified specific brain regions that express isoforms of these two signalling proteins. In these specific brain regions they fulfil until now unknown, specialised and unique functions. In addition, novel signalling routes were discovered that enable differential effects of Semaphorin-Plexin signalling in brain regions during distinct developmental stages. Lastly, the contribution of Plexins to human developmental disorders was examined. Together, this thesis contributes to a better understanding of the complex signalling of Semaphorins and Plexins during the growth of axons to ensure correct brain development in health and disease.