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Authors & Affiliations
Charles Gora, Samer Hussein, Emmanouil Metzakopian, Martin Lévesque
Abstract
Midbrain dopaminergic (mDA) neurons play important roles in controlling a variety of brain functions. An abnormal development of the dopaminergic circuits can lead to different brain disorders. In addition, degeneration of mDA neurons is the leading cause of Parkinson’s disease. Dopamine neurons in the midbrain form a heterogeneous set of neurons that innervate different regions of the brain. However, the developmental mechanisms regulating the precise organization of these neuronal circuits remain poorly understood. Recent discoveries have revealed that a proportion of the proteins used for the navigation of developing axons are produced locally in axons. This project aims to reveal the cellular and molecular mechanisms regulating the precise development of dopaminergic sub-circuits. To identify mRNAs locally translated in mDA axons, we used transgenic mice in which ribosomes in mDA neurons are specifically tagged (RiboTag mice). Using these mice, we isolated mRNAs associated with the ribosomes in mDA axons innervating different brain regions and at different developmental time points. Analysis of axonal mRNA content was performed by RNA-sequencing. Our results indicate that specific set of mRNAs are present in axons innervating the striatum, the nucleus accumbens or the prefrontal cortical areas. We are now validating and study the role of axon guidance molecules present in mDA axons. In addition to uncover the axonal translatome of the dopaminergic system, this project help to better understand the development of the dopaminergic circuits.