37th Cycle Kick-Off Speaker: Prof. Claudia Bagni

Molecular Complexes Underlying Motor and Social Skill Development

Motor and social disturbances have been widely observed in children with different neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) and Fragile X Syndrome (FXS). Identifying the molecular mechanisms underlying these phenotypes has become key for a better understanding of the pathophysiology of the disease and the development of novel therapeutic strategies.
Today, mutations in hundreds of genes and genomic copy number variations (CNVs) contribute significantly to ASD susceptibility. CNV at the 15q11.2 region has been identified as a significant risk region for neuropsychiatric disorders, including ASD.
One gene in this region is CYFIP1, encoding the Cytoplasmic FMR1 Interacting Protein 1. To understand the molecular dynamics underlying the development of motor skills and social behavior, my laboratory uses mice, flies and human cells mutated for this gene to understand molecular dynamics underlying the development of motor skills and social behavior.
Here, I will discuss how CYFIP1 haploinsufficiency in mice causes delayed growth and arborization of callosal axons, deficits in functional brain connectivity, and affects ASD-related behavior and the molecular and cellular mechanisms underlying those deficits. Finally, I will discuss a novel molecular mechanism of how mitochondrial metabolism contributes to developing the social brain in flies and mice.
Altogether, our results suggest that mitochondrial alterations may be at the basis of the sociability and motor coordination deficits observed in patients with ASD, opening new therapeutic avenues for ASD and other neurodevelopmental disorders.