Protocadherin 19 (PCDH19) is an X-linked gene that is primarily expressed in the developing central nervous system and is thought to act as a homotypic cell-cell adhesion molecule. Mutation of PCDH19 in humans causes PCDH19 Girls Clustering Epilepsy (PCDH19 GCE) which displays an unusual inheritance pattern; females heterozygous for PCDH19 mutations are affected and homozygous males are spared. This has led to the hypothesis that a mixture of PCDH19-wild type and PCDH19-null cells causes abnormal neuronal connections leading to disease. This hypothesis has been termed the “cellular interference model", but lacks supporting evidence. To investigate the "cellular interference model" we generated a PCDH19-epitope tagged (Pcdh19-TAG) mouse using CRISPR-CAS9 technology allowing us, for the first time, to characterise PCDH19 expression in the developing mouse brain. Furthermore we crossed Pcdh19-TAG mice with a Pcdh19 null mouse to create a mixture of Pcdh19-WT and Pcdh19-null cells and observed striking segregation between these populations in the developing and postnatal cortex. Segregation occurs in both the excitatory and inhibitory neural progenitor cells of the cortex, potentially resulting in aberrant cortical lateral connections and interneuron distribution which may contribute to the abnormally elevated brain activity we observe in Pcdh19 heterozygous mice. This research provides the first evidence supporting the ‘cellular interference’ model as the molecular mechanism causing PCDH19 GCE. Furthermore we have shown that PCDH19 is expressed throughout neural development and acts as a homotypic cell-cell adhesion molecule where it is important for correct cell patterning of the cortex.