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Autophagy is required for midbrain dopaminergic axon development and their responsiveness to guidance cues

M.S. Profes, A. Saghatelyan, M. Lévesque
doi: https://doi.org/10.1101/2020.10.09.333435
M.S. Profes
1Department of Psychiatry and Neurosciences, Faculty of Medicine, Université Laval, Québec, Quebec G1V 0A6, Canada
2CERVO Brain Research Centre, 2601, chemin de la Canardière, Québec, Quebec, Canada G1J 2G3
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A. Saghatelyan
1Department of Psychiatry and Neurosciences, Faculty of Medicine, Université Laval, Québec, Quebec G1V 0A6, Canada
2CERVO Brain Research Centre, 2601, chemin de la Canardière, Québec, Quebec, Canada G1J 2G3
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M. Lévesque
1Department of Psychiatry and Neurosciences, Faculty of Medicine, Université Laval, Québec, Quebec G1V 0A6, Canada
2CERVO Brain Research Centre, 2601, chemin de la Canardière, Québec, Quebec, Canada G1J 2G3
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  • For correspondence: martin.levesque@fmed.ulaval.ca
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Abstract

Mesodiencephalic dopamine (mDA) neurons play a wide range of brain functions. Distinct subtypes of mDA neurons regulate these functions but the molecular mechanisms that drive the mDA circuit formation are largely unknown. Here we show that autophagy, the main recycling cellular pathway, is present in the growth cones of developing mDA neurons and its level changes dynamically in response to guidance cues. To characterize the role of autophagy in mDA axon growth/guidance, we knocked-out (KO) essential autophagy genes (Atg12, Atg5) in mice mDA neurons. Autophagy deficient mDA axons exhibit axonal swellings and decreased branching both in vitro and in vivo, likely due to aberrant microtubule looping. Strikingly, deletion of autophagy-related genes, blunted completely the response of mDA neurons to chemo-repulsive and chemo-attractive guidance cues. Our data demonstrate that autophagy plays a central role in regulating mDA neurons development, orchestrating axonal growth and guidance.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 09, 2020.
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Autophagy is required for midbrain dopaminergic axon development and their responsiveness to guidance cues
M.S. Profes, A. Saghatelyan, M. Lévesque
bioRxiv 2020.10.09.333435; doi: https://doi.org/10.1101/2020.10.09.333435
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Autophagy is required for midbrain dopaminergic axon development and their responsiveness to guidance cues
M.S. Profes, A. Saghatelyan, M. Lévesque
bioRxiv 2020.10.09.333435; doi: https://doi.org/10.1101/2020.10.09.333435

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