Loss of Eml1 alters microtubule-associated protein networks in mouse brain heterotopia

The layered structure of the cerebral cortex is formed through a complicated sequence of highly controlled stages. During this process, the perturbations of neuronal migration and cell division can result in a rare disorder called cortical heterotopia. Heterotopia patients can have recurrent epileptic seizures, developmental delays, and mild intellectual disabilities. Studying heterotopia has been challenging because human mutations linked to the disease often do not result in heterotopia formation in mouse models. EML1 is a microtubule-binding protein, and it stands out as the first heterotopia-associated gene where mutations lead to heterotopia formation in both humans and mice. In this study, we conducted a comparative proteomic analysis of the Eml1 cKO heterotopic mice cortices and neuronal progenitor primary cells during cerebral cortex development. We performed label-free and dimethyl labeling-based quantitative proteomic approaches, and microtubule pelleting assays to understand how Eml1 depletion disrupts protein networks in cortical tissue and neuronal progenitor primary cells during cerebral cortex development.