Cortical development and disorders

Cortical neuronal cell development starts at about 7 weeks’ gestation from stem cells in the germinal matrix that line the ventricles. The stem cells proliferate and differentiate into glial cells and neurons. The glial cells migrate radially to the brain surface and create a scaffold for the neurons to follow to the outer cortex, where the neurons organize connections and commissures. Other neurons derived from the ganglionic eminence migrate tangentially to form inhibitory neurons and basal ganglia. Rapid development occurs at about 15 to 20 weeks’ gestation. By about 30 weeks’ gestation, neuron development is completed, resulting in the six cortical layers. Neurons are formed in larger numbers than needed, and more than half undergo apoptosis. At the same time as the cortex is being formed, other brain structures develop, including the commissures (e.g., corpus callosum), cerebellum, and eyes. Interruption in normal neurodevelopment from any cause can result in abnormalities of any of these structures, and the final clinical manifestations often reflect the timing rather than the nature of the insult. Migration and development are controlled by complicated gene-protein interactions. Genes controlling neural development often also control the development of other body organs such as muscles and bones. Mutations or disturbances to genes involved in neurogenesis can result in abnormal somatic development. For example, mutation in the FGRF3 gene associated with thanatophoric dysplasia results in both skeletal abnormality and cerebral pachygyria.