Development of bilateral circuits of the nervous system: From molecular mechanisms to the cerebellum and its implication in neurodevelopmental disorders

Abstract

The brain is the most complex organ we have, and it is the one that defines us as human beings. It is the basis of intelligence, of our thoughts and memories. In addition, it interprets the world through the senses, initiates movement and controls our behaviors. The correct functioning of this organ is based on the correct establishment of connectivity patterns between the millions of neurons which enable a precise and efficient communication between them. These neural networks emerge during embryonic and postnatal development. The formation of proper neuronal circuitry relies on diverse and very precisely orchestrated events controlled by specific molecular mechanisms. Therefore, failures in these early events will lead to brain pathologies and complex disorders. In the last decades, remarkable progress has been made in identifying and in understanding the mechanisms of action of the molecular that direct axon and neural circuitry development. However, their role in vivo in many aspects of neural circuit formation remains largely unknown, particularly how the impairment of this initial connectivity derives in complex neurodevelopmental pathologies. Here, I highlight part of my contributions and recent advances that shed light on the complexity of mechanisms that regulate axon guidance and the wiring of the bilateral circuits of the central nervous system. Furthermore, I discuss about how understanding the development of bilateral circuits of the cerebellum is essential to understand the emergence of diverse neurodevelopmental pathologies.