Project: Decrypting Cadherin-13 function in cortico-cerebellar circuitry underlying neurodevelopmental disorders!

Acronym	DECODE! (Reference Number: NEURON-117)
Project Topic	Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by deficits in social skills and communication, stereotyped and repetitive behavior, and a range of alterations in cognitive function. ASD shows high heritability and comorbidity with other disorders such as intellectual disability and attention-deficit/hyperactivity disorder. The recent progress in human genetics have led to the identification of hundreds of genes associated with autistic-like behaviors, including a growing number of genes encoding synaptic proteins. Recently, rare de novo and inherited deletions at the CDH13 locus have been linked to ASD1,2, indicating the clinical relevance for loss-of-function mutations in CDH13. Although CDH13 has been characterized as an adhesion protein in non-neuronal cells, surprisingly little is known about its function in the brain. In DECODE! we will develop mouse models to study the cell- and circuit-specific effects of CDH13 deficiency. In particular, we will focus on the cortico-cerebellar circuitry, which recently has been implicated in ASD. In addition we will harness the potential of human induced pluripotent stem cells (iPSC) to characterize CDH13 dysfunction in patient iPSC-derived cultured inhibitory neurons at the molecular and cellular level. Understanding circuit-specific alterations caused by CDH13 deficiency in mouse and human models may ultimately help us designing targeted treatment of specific ASD symptoms.
Network	NEURON Cofund
Call	Call for Proposals for Transnational Research Projects on Mental Disorders

Project partner

Number	Name	Role	Country
1	Stichting Katholieke Universiteit Nijmegen	Coordinator	Netherlands
2	University of Wuerzburg	Partner	Germany
3	Centre de Recherche du CHU Ste.Justine/Université de Montréal	Partner	Canada
4	UMR5203	Partner	France