Genetic changes (mutations) in the gene Protocadherin-19 (PCDH19) - located on the X-chromosome - are associated with Epileptic Encephalopathy Early Infantile 9 (EIEE9), a rare genetic disease that causes early onset epilepsy and cognitive impairment in heterozygous females (females that carry a normal and a mutant copy of PCDH19). To date, little is known about how this phenomenon causes EIEE9, however the early onset of the disorder suggests a neurodevelopmental basis. Using genetically-altered mice, we have shown that Pcdh19 has a critical role in brain development by helping primordial brain cells called progenitors communicate with each other and transition into mature nerve cells, an event called neurogenesis. We also found that progenitors that express Pcdh19 and progenitors that do not express Pcdh19 produce significantly less and more nerve cells, respectively, but only in the developing brains of heterozygous female mice, which may be the underlying factor of EIEE9. To explore this further, we aim to discover the significant molecular pathways that Pcdh19 might be involved in to regulate neurogenesis using candidate and unbiased approaches. The results from this project will provide new insight into the roles of Pcdh19 during brain development and highlight potential targets for EIEE9 therapeutic intervention.