Tuesday, 7 March 2017

The connectome: here is how local microRNAs help axons find their way to their target

A CIBIO research team led by ML Baudet has identified a fundamental mechanism of brain wiring. The full study in Cell Reports.

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A study coordinated by Marie-Laure Baudet of CIBIO – University of Trento, recently published in Cell Reports, identified one of the basic processes in the formation of neuronal connections. The study describes how microRNAs help axons interpret the messages from the environment so that they can reach their right target.

Il team di ricerca del CIBIO (Foto ©RobertoBernardinatti per UniTrento)During brain development, neurons extend protrusions called axons whose task is to connect neurons to their target cells. Axons have a long distance to cover to reach their target cells in a very complex environment. How do axons know where to go? Like in the tale of Little Thumb, they manage to find their way thanks to “chemotropic” molecules (the breadcrumbs along the path) which guide them precisely to their final destination.

The study demonstrates the fundamental role of microRNAs in recognizing the right path encoded by these chemotactic molecules. Micro-RNAs are small molecules of ribonucleic acid that are involved in a number of physiological processes both in plants and in animals. If a specific microRNA is experimentally removed from an axon, the latter loses its ability to interpret the signals it receives from the environment. Not knowing where to go, the axon fails to reach its target and establishes aberrant neuronal connections.

The development of connections among neurons is absolutely essential during brain development. These connections, once formed, create a network of neural circuits which are the basis of all brain activity, from the basic processing of sensory information to higher cognitive functions such as decision-making. A failure in this phase, during the creation of the circuits, can have devastating consequences and may lead to serious cognitive and behavioral disorders. Unravelling the molecular mechanisms that lead to the formation of neural circuits is therefore critical to further our understanding of these pathologies and to inform the development of novel clinical therapies.

These key findings come after 5 years of collaboration with the University of Cambridge, where Marie-Laure Baudet worked until 2012. The researcher then moved to Italy, where she founded her own research laboratory at CIBIO in Trento, thanks to the Career Development Award Program of the Armenise-Harvard Foundation. The laboratory is currently receiving funding from the US Armenise-Harvard Foundation, the European Commission, and the Italian Ministry of Education, Universities and Research (MIUR).