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NINTCORDEV SIGNED

NIPBL and Integrator function and dysfunction in human cortical development

Total Cost €

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EC-Contrib. €

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Partnership

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Project "NINTCORDEV" data sheet

The following table provides information about the project.

Coordinator
ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM 

Organization address
address: DR MOLEWATERPLEIN 40
city: ROTTERDAM
postcode: 3015 GD
website: www.erasmusmc.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 177˙598 €
 EC max contribution 177˙598 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2018
 Duration (year-month-day) from 2018-05-01   to  2020-08-21

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM NL (ROTTERDAM) coordinator 177˙598.00

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 Project objective

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. This will be accomplished by creating patient-specific INTS1, INTS8 and NIPBL mutations in human pluripotent stem cell lines, which will be differentiated into neural progenitor cells to assess effects on protein-protein interactions, long-range chromosome contacts and RNApol2 pausing and into cerebral organoids to assess the impact on different aspects of the neurodevelopmental program, including progenitor proliferation, neuronal migration and subtype specification.

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The information about "NINTCORDEV" are provided by the European Opendata Portal: CORDIS opendata.

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