Autophagy controls neuronal differentiation by regulating the WNT/DVL signal pathway

Disruption of autophagy might lead to failure in the downregulation of WNT signaling and consequently, delaying neuronal differentiation. Dysregulation of autophagy has been associated with a variety of neurological diseases, including Vici syndrome. Here, we developed cerebral organoids culture to model Vici syndrome by introducing loss of function mutation in EPG5 gene.

Mutation in EPG5 gene disturbed autophagy process, subsequently induced defect in progenitor cells migration and cortical layer generation in organoids. The results showed how damaged autophagy leads to smaller organoids, recapitulating Vici syndrome-associated microcephaly, and therefore validating the disease relevance of our study.