Cortical neural development in health and disease

Understanding how the mammalian brain develops is the sine qua non condition for deciphering neurodevelopmental disorders (ND), a condition characterized by an abnormal brain development in utero and leading to intellectual and/or motor disabilities in juveniles. The main structure affected in ND is the cerebral cortex. It is composed of six layers of neurons that are sequentially generated from progenitor cells (PC) during embryonic life. This patterning if altered results in malformations of cortical development (MCD) associated with ND clinical manifestations. Despite progress in MCD diagnosis, the cellular mechanisms regulating the sequential acquisition of PC identity and the orderly buildup of cortex remain poorly understood. Based on MCD mouse model and promising results obtained on X-ray holographic nanotomography on embryonic cortex slices, this proposal aims to continue the coordinated study of PC structure and physiology in health and disease.