Morphological Alterations During Early Development: Validating the Zebrafish Model for Xia-Gibbs Syndrome

• Grant number: 25/02334-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: April 20, 2025
• End date: July 24, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ana Cristina Victorino Krepischi
• Grantee: Davi Mendes Campos Fialho
• Supervisor: Aaron Scott
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University College London (UCL), England
• Associated to the scholarship: 23/16839-1 - TRANSCRIPTOMIC STUDY OF A ZEBRAFISH MODEL TO INVESTIGATE THE PATHOPHYSIOLOGICAL MECHANISMS OF XIA-GIBBS SYNDROME, BP.IC

Abstract

We present an internship BEPE proposal for studying morphological alterations during early development using a zebrafish model for Xia-Gibbs Syndrome (XGS). XGS is a rare neurodevelopmental disorder linked to mutations in the AHDC1 gene. The study aims to understand how these mutations affect development, using zebrafish due to its genetic and developmental similarity to humans. A zebrafish model with a heterozygous indel variant in the ahdc1 gene was previously developed in Brazil using CRISPR-Cas9. Preliminary results show reduction in ahdc1 expression and delayed pigmentation in homozygous mutants, suggesting disruptions in pigmentation pathways or neural crest cell migration. The internship will be conducted at the Wilson Lab at University College London, known for expertise in eye formation and neurodevelopment using zebrafish models. Due to time constraints, the knockout model will be reproduced at the Wilson Lab instead of transporting animals from Brazil. The student will learn CRISPR/Cas9 knockout techniques and conduct morphological phenotyping using immunohistochemistry and confocal imaging. This includes designing guide RNAs, validating knockouts, and analysing brain and eye morphology. The internship will enhance the student's technical skills and contribute to a deeper understanding of XGS. It supports future research directions for the student, who intends to pursue graduate studies in this field. Activities are scheduled from March to June 2025, including guide RNA design, CRISPR injections, knockout validation, and morphological analyses.