GUIDANCE-MIR · microRNAs: ROLES IN AXON GUIDANCE DURING BRAIN WIRING

The precise elaboration and specification of neuronal circuits is at the basis of any properly functioning nervous system. For circuits to be established, neurons form remarkably accurate connections with their target cells during development. How are these connections established? Neurons send out cell protrusions called axons, which navigate in a complex environment to reach their exact target, a process known as axon guidance or pathfinding. Understanding the key molecules that induce the formation of such precise circuits is crucial, because any failure in this process, either during development or following injury or disease, impairs the proper function of the nervous system. Such precision is achieved by tight regulation, in space and time, of guidance molecules and their concomitant signalling mechanisms. However the key molecules involved in this highly accurate regulation are to date largely unknown. Very recent findings have suggested that specific microRNAs (miRNAs) could be involved in this process. Indeed, I have shown that miR-124 contributes to regulating with high precision the temporal expression of receptor to cue and, with collaborators, that miR-134 is implicated in the turning response of axons. However the possibility that miRNAs play a crucial role in axon guidance is to date unknown. In addition, prediction algorithms strongly suggest that many miRNAs could be implicated in this process. Indeed, hundreds of miRNAs have been sequenced to date including many detected within the nervous system, but very few have known functions. I therefore propose to investigate whether and which miRNAs are key regulating molecules in axon guidance.