NIPBL and Integrator function and dysfunction in human cortical development

Project summary

Cornelia de Lange Syndrome is highlighted by intellectual disability and seizures and most frequently caused by mutations in the cohesin loading factor NIPBL. Previous work showed that NIPBL interacts with the neuronal transcription factor Zfp609 and the Integrator complex to regulate cortical neuron migration. Furthermore, INTS1 and INTS8 mutations were recently reported to cause a severe neurodevelopmental syndrome in humans. This proposal aims to identify the human neuro-developmental defects caused by INTS1 and INTS8 mutations and NIPBL haplo-insufficiency and molecularly dissect the affected transcriptional processes.