NIPBL and Integrator function and dysfunction in cortical development
| Title | NIPBL and Integrator function and dysfunction in cortical development |
|---|---|
| Acronym | NINTCORDEV |
| Start date | 2018-05-01 |
| End date | 2020-04-30 |
| Sponsor | Marie Skłodowska-Curie Action (MSCA) |
| Institution | Erasmus MC |
Associated cell lines
Project Description
Development of the cortex requires intricate orchestration of progenitor self-renewal and neuronal differentiation, subtype specification, migration and integration in neuronal circuits. Disturbance of any of these processes has been linked to a variety of developmental disorders, including Cornelia de Lange Syndrome (CdLS). CdLS is highlighted by intellectual disability and seizures and most frequently caused by mutations in the cohesin loading factor NIPBL. Our previous work showed that Nipbl interacts with the neuronal transcription factor Zfp609 and the Integrator complex to regulate cortical neuron migration in mouse embryos. Furthermore, INTS1 and INTS8 mutations were recently reported to cause a severe neurodevelopmental syndrome in humans. This proposal aims to identify the human neurodevelopmental defects caused by INTS1 and INTS8 mutations and NIPBL haploinsufficiency and molecularly dissect the affected transcriptional processes.