Investigation of the role of Netrin receptors in the cortical disorganization in a monogenic type of autism using cellular models

• Grant number: 24/20077-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fabio Papes
• Grantee: Gustavo Duarte Verçosa
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 22/12762-1 - Investigation of alterations in neuronal migration in an autism spectrum disorder using human cellular models and animal models, AP.TEM

Abstract

This project aims to investigate the role of Netrin-1 and its receptors from the UNC5 family in controlling neuronal migration in an Autism Spectrum Disorder (ASD). Neuronal migration is crucial for the formation of the cerebral cortex, involving the radial and tangential movement of neurons during embryonic development. Changes in neuronal migration can compromise the formation of neural circuits and the individual's cognitive and motor functions. The Netrin-1 protein plays a fundamental role in guiding migrating neurons, interacting with UNC5 receptors, which promote the repulsion of neuronal cells until they reach their final positions in the neural tissue. In this study, Pitt-Hopkins Syndrome (PTHS), a monogenic type of ASD caused by mutations in the TCF4 gene, will be used as a model to explore how genetic mutations can impact neuronal migration in the context of autism. To this end, we will perform the manipulation of patient-derived cells and microscopic analyses to study the role of UNC5 receptors in the alterations in neuronal migration observed in this type of ASD. Our project aims to identify aspects of the syndrome's pathophysiology that could guide the future development of specific therapies, benefiting not only patients with Pitt-Hopkins Syndrome, but also other neuropsychiatric conditions characterized by failures in neuronal migration.