Projet européen ERA-NET

Laurent Nguyen’s lab involved in research about neurological causes of autism

Disruption of the spatio-temporal dialogue between migrating cortical neurons as underlying factor in Autism Spectrum Disorder

Although the precise etiology of Autism Spectrum Disorder (ASD) is unknown, one of the most accepted theories is an abnormal proportion of excitatory projection neurons (PNs) and inhibitory cortical interneurons (cINs). During cortical development, migrating PNs and cINs interact in such a way that impaired migration of each of these major classes of neurons affects the number and location of the other.

In the present project, researchers propose an impaired spatio-temporal crosstalk between migrating PNs and cINs as shared pathomechanism in ASD. They will test this hypothesis by studying several ASD-linked genes (Cntnap2, FMR1, Agtpbp1) involved in neuronal migration of PNs and/or cINs at different levels, which all show increased PNs/cINs ratio. They will carry out a multidisciplinary approach to study different systems, from animal models to state of the art in vitro cultures including ‘next generation’ patient-derived brain organoids harboring mutations in each of these ASD-associated genes. They will characterize the contribution of these genes to the reciprocal interaction of migrating PNs and cINs by conditionally deleting them in each of these major classes of neurons in animal models. Brain organoids will be used to study patient’s molecular and cellular specific features and their contribution to the abnormal circuit wiring. In short, we will be able provide important new insights into a potential new signature driving neurodevelopmental pathological mechanisms in autism.

Project Coordinator

PhD Olga Penagarikano, Pharmacology, University of the Basque Country, Leioa, Spain

Project Partners

PhD Laurent Nguyen, Neuroscience, University of Liege, Liege, Belgium

PhD Jean Bernard Manent, Neurobiology, INMED INSERM, Marseille, France

Dr. Silvia Cappello, Psychiatry, Max Planck Institute, Munich, Germany



About NEURON, the european funding network

European Research Area Networks (ERA-NETs) are projects funded by the European Commission in various research fields. Their goal is to create a European Research Area in which research is conducted and funded across countries, allowing research groups to jointly work on specific problems, exchange ideas, and benefit from cross border expertise. The Network of European Funding for Neuroscience Research (NEURON) was initiated in 2003.

To-date 25 funding organisations from 14 EU countries, Israel and Turkey as EU-associated countries, and Norway and Canada participate in NEURON Cofund:
Austria (FWF), Belgium (FNRS/Flandern, FWO), Canada (CIHR, FRQS/Québec), Finland (AKA), France (ANR, INSERM, CNRS), Germany (DLR-PT/BMBF), Israel (CSO-MOH), Italy (MOH), Latvia (VIAA), The Netherlands (NWO), Norway (RCN), Poland (NCBR), Portugal (FCT), Romania (UEFISCDI), Slovakia (SAS), Spain (ISCIII, MINECO), United Kingdom (MRC), Turkey (TÜBITAK).

Research into the human brain and its diseases is one of the key challenges of the 21st century. Among the many diseases affecting health, disorders of the brain are major causes for impaired quality of life and increasing health care costs. Despite some progress in understanding the molecular mechanisms of various neurological and psychiatric disorders, research is still far from being able to offer solutions to conquer them. In addition, the development of curative treatments or prevention strategies has not been, to date, very successful. A concerted effort of funding organisations and of research groups in this area, is thus needed to reach the long term goal of curing patients with disorders of the brain and nervous system, and helping their relatives.

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