Molecular Mechanisms of Cortical Development (360G-Wellcome-204021_Z_16_A)

EIEE9 (Early Infantile Epileptic Encephalopathy 9) is a rare genetic condition caused by mutations in the PCDH19 (Protocadherin 19) gene. The disorder affects heterozygous females and is characterized by epileptic seizures and cognitive impairment. PCDH19 is a cell-adhesion molecule that mediates cell-cell interactions during cortical development and it is thought to play an important role in neuronal migration and synapse formation. Researchers think the disease is caused by "cellular interference": PCDH19 is located on the X chromosome and - due to random X-inactivation - heterozygous females have a mixed population of PCDH19 positive and negative cells which are unable to correctly interact with each other leading to defective circuit formation and disease. We aim to create a transgenic mouse model that will enable selective labelling of PCDH19 expressing cells. This mouse model will be a valuable tool to investigate interactions between PCDH19+ and PCDH19- cells during cortical development and to study circuit formation. We will combine our transgenic mouse with recently developed techniques for synaptic tracing to characterize the neuronal circuits in which PCDH19+ neurons are involved by identifying those neurons that connect to PCDH19+ cells.