Our brain processes information and determines our daily functioning. Growing and developing a brain requires great precision in the creation, docking and positioning of nerve cells. What is the consequence for this precision in making if the NIPBL gene, a key regulator in making cells, malfunctions. We already know that several genes play a role in Cornelia de Lange syndrome (CdLS). The illustration below shows that NIPBL, the gene altered (mutated) in the vast majority of CdLS cases, plays a role in the so-called Cohesin Complex. We know that in people with CdLS we often see the following: So it is interesting to better understand ; A recent discovery has made it possible to recreate a piece of nerve tissue like the brain using 'pluripotent stem cells'. We call this 'brain organoids', which are nerve cells in 3D or 'mini-brains'. For example, by taking a piece of skin from people with CdLS (who have a NIPBL mutation and a mosaic NIPBL mutation in particular), the researchers can "reprogramme pluripotent stem cells" from that tissue to become, for example, a heart muscle, blood stem cells, a pancreas but also nerve cells from the brain. Thus, researchers can thus make brains in a dish, which they can study well for the influence of a mosaic NIPBL mutation. She managed to grow human brain organoids that allow us to investigate how structures of particular brain regions are formed, similar to what happens in the very early stages of a human embryo. She will manage the interactions with the patients/caretakers and the CdLS family organization and help to collect tissue samples. Mehrnaz Ghazvini and her team from the iPS core facility will derive induced pluripotent stem cells from patient samples, which we need to grow the organoids. Together, we want to understand how mutations in the NIPBL gene affect the proper development of the human brain. An important aspect is to find out how brain development is affected when only a few cells have the mutation (mosaicism).Cause of Cornelia de Lange syndrome
Changes in the brain
Better Understanding
How can we look at this?
Making a piece of the brain in a dish
Research team and supporters
Debbie is Professor - Principal Investigator of the Erasmus MC, Cell Biology
Sylvia is Clinical Supervisor and Trainer of the Zodiak-Prinsenstichting, MD PhD at expertise centre Cornelia de Lange syndrome, Medical Director at Vereniging Cornelia de Lange syndroom, (MD) Physician for ID, SIB & CdLS at International Scientific Advisory Council (SAC)
Mehrnaz is Head iPS core facility of the Erasmus MC, iPS core facility
Kerstin is Lid van de SAC of the Vereniging Cornelia de Lange syndroom, Molecular Genetics Research at International Scientific Advisory Council (SAC), Professor - Principal Investigator at Erasmus MC, Cell Biology
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