Abstract
Neuronal numbers and the associated size of the cerebral cortex, surface folding and laminar organisation are determined by precise developmental mechanisms that are orchestrated by several intrinsic and extrinsic molecules. Abnormalities during development can cause manifold microscopic and macroscopic cortical malformations, mostly accompanied by clinical consequences such as mental disorders, intellectual disabilities, or epileptic seizures. Most cortical malformations and associated neurological disorders result from genetic defects, however the cellular mechanisms remain complex and poorly understood. Eph receptor tyrosine kinases and their ligands, the ephrins, are abundantly expressed in the developing brain where they regulate several developmental processes that are crucial for correct brain formation. Ephrin family members represent membrane-bound proteins that are key players in complex short-range cell-cell communication. In addition, mechanisms for long-range interactions have been described recently. Several ephrins have already been shown to control cell cycle dynamics of cortical stem cells during corticogenesis and the positioning of postmitotic neurons. In addition, mutations in genes encoding for members of the Eph/ephrin family are implicated in mental disorders, although the underlying mechanisms remain to be elucidated. A deeper understanding of Eph/ephrin interactions during cerebral cortex development will be beneficial to shed light on developmental disabilities. Here, we discuss the function of Eph/ephrin system during the different processes of corticogenesis and the impact on cerebral malformations.