Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects millions of people worldwide. Many autistic individuals experience sensory differences, such as increased sensitivity to touch, temperature, or pain. These differences may be related to alterations in the brain, the peripheral nervous system, or both, but the underlying biological mechanisms remain poorly understood. This project aims to investigate the development and function of peripheral sensory neurons in autism using stem cell technology, focusing on neural crest progenitor cells (NCPCs) and how early developmental alterations may affect sensory neuron function.

Previous work from our partner laboratory in Brazil showed that NCPCs derived from autistic individuals exhibit altered proliferation, suggesting abnormal cell cycle regulation. Building on these findings, this project aims to determine whether these changes are associated with replication stress, altered DNA replication dynamics, and DNA damage, and whether similar mechanisms are present in individuals with macrocephalic ASD. The project will also investigate the molecular pathways involved in these alterations and evaluate whether they persist during neuronal differentiation, potentially contributing to functional changes in peripheral sensory neurons, including altered synaptic activity and electrophysiological properties.

The findings from this research may improve our understanding of the cellular and molecular mechanisms underlying ASD. In the long term, this knowledge could contribute to the identification of potential biomarkers and the development of more targeted therapeutic strategies.