E3 ubiquitin ligases and cerebral cortex development in health and disease.

Cerebral cortex development involves the sequential progression of biological steps driven by molecular pathways whose tight regulation often relies on ubiquitination. Ubiquitination is a posttranslational modification involved in all aspects of cellular homeostasis through the attachment of a ubiquitin (Ub) moiety on proteins. Over the past years, an increasing amount of research has highlighted the crucial role played by Ub ligases in every step of cortical development and whose impairment often leads to various neurodevelopmental disorders. In this review, we focus on the key contributions of E3 Ub ligases for the progression of the different steps of corticogenesis, as well as the pathological consequences of their mutations, often resulting in malformations of cortical development. Finally, we discuss some promising therapeutic strategies for these diseases based on recent advances in the field.