Investigating the role of Ephrin receptors in the neuronal migration process in a monogenic autism spectrum disorder

• Grant number: 24/18719-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2025
• End date: January 31, 2027
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fabio Papes
• Grantee: Nicolas Gasparine Figueiredo
• 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

Autism Spectrum Disorders (ASD) are neurodevelopmental diseases characterized by behavioral and motor abnormalities. Some types of ASD are monogenic, that is, caused by mutations in just one gene. This is the case of Pitt-Hopkins Syndrome (PTHS), whose molecular etiology involves de novo mutations in the TCF4 gene. Preliminary results obtained by our group revealed changes in the process of neuronal migration in the nervous tissue of patients with PTHS. Furthermore, in neurons and organs derived from patients with PTHS, we observed a decrease in the expression of genes coding for chemotactic molecules that control migration, including Ephrins (EFN genes) and their receptors (EPHA genes). The EPHA family encodes type A Ephrin receptors, which mediate cell-cell interactions, playing a fundamental role during cellular migration. The current project will use in vitro 2D cultures of neurons derived from patients with PTHS, with the aim of investigating the relationship between altered neuronal migration in the PTHS nervous tissue and the decrease in the expression of EPHA genes. Furthermore, we will evaluate whether the recovery of EPHA gene expression can reverse the neuronal migration deficit in the type of ASD under investigation. The scientific knowledge gained in this project will reveal the molecular and cellular mechanisms of PTHS and may lead to the development of specific therapeutic methods for this and other diseases characterized by migration defects.