Manipulation of TCF4 gene expression to assess its necessity in neuronal migration using in vitro cellular models.

• Grant number: 24/12825-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Fabio Papes
• Grantee: Breno Braga Hernandes
• 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 comprise a group of neuropsychiatric illnesses caused by problems during neurodevelopment and characterized by altered social behavior, impaired communication and repetitive behavioral patterns. Clinical and neuropathological evidence obtained over the last decade points to abnormalities in the development of the cerebral cortex suggestive of defects in neuronal migration. In this research project at the Scientific Initiation level, we will use neuronal cultures to test antisense oligonucleotide-mediated knockdown of the expression of TCF4, a gene mutated in patients with an autism spectrum disorder known as Pitt-Hopkins Syndrome. Also, these cellular models will be investigated via qPCR to determine whether TCF4 knockdown is sufficient to alter the expression of neuronal migration markers. The project will contribute to the discovery of new pathological mechanisms in autism, in conjunction with the experiments in dimension #2 of the associated Thematic Project.