Zinc quantitative imaging in the axon initial segment: involvement of zinc homeostasis in neurodevelopment and autism

Zinc dyshomeostasis (deficiecy) contributes to the etiology of autism, although the molecular mechanisms involved are largely unknown. Our research consortium has identified the Zn-protein Prickle 2 (Pk2) as a critical neuronal polarity determinant and has shown that it participates in the early assembly of the axon initial segment. Pk genes are strong autism and epilepsy candidates. The aim of this experiment is to test the hypothesis that Zn homeostasis and Pk2 signalling converge during the formation of the axon and its initial segment. Thanks to the nano-correlative imaging of metals and proteins in neurons that we developed using STED super resolution microcopy and synchrotron nano-XRF, we will compare the quantitative distribution of Zn and Pk2 clusters in the axon initial segment at different stages of neurodevelopment. These results will serve as basis for further studies on Zn supplementation in Pk2 depleted models for the treatment of autism.