Protocadherin 19 in cortical development

Year of award: 2015


  • Dr Isabel Martinez Garay

    Cardiff University

Project summary

Mutations in protocadherin-19 (Pcdh19), a delta-2 protocadherin encoded on the X chromosome, lead to epilepsy with cognitive impairment in heterozygous females. The early onset of disease suggests a neurodevelopmental basis for the disorder, but the function of this gene is entirely unknown.

We propose to use the developing mouse brain to analyse the role of Pcdh19 in neurogenesis, migration and circuit formation. Data from expression studies, anatomical analyses and the unusual inheritance mode of the disorder, where hemizygous males are unaffected, support the theory that Pcdh19 plays a role in these processes. We will first perform a comprehensive molecular and hodological characterisation of Pcdh19 expressing cells at different developmental stages. We will then analyse a Pcdh19 null mouse mutant and assess whether neurogenesis and/or migration are affected. We will directly interfere with Pcdh19 function using in utero electroporation, either by shRNA to cause an acute reduction of its levels or with mutant forms of the protein. Analysing synapses in embryonic stem cell-derived neurons and electrophysiological recordings in brain slices will complete the analysis.

Our results will provide insight into the roles of Pcdh19 during corticogenesis and form a useful basis for subsequent studies.