PT  - JOURNAL ARTICLE
AU  - Profes, M.S.
AU  - Saghatelyan, A.
AU  - Lévesque, M.
TI  - Autophagy is required for midbrain dopaminergic axon development and their responsiveness to guidance cues
AID  - 10.1101/2020.10.09.333435
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.09.333435
4099  - http://biorxiv.org/content/early/2020/10/09/2020.10.09.333435.short
4100  - http://biorxiv.org/content/early/2020/10/09/2020.10.09.333435.full
AB  - 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 StatementThe authors have declared no competing interest.