Wesley S. Ercanbrack Austin Dungan Ella Gaul Mateo Ramirez Rebecca A. Wingert ^*

• University of Notre Dame, Notre Dame, United States

Friedreich's Ataxia (FRDA) is the most common hereditary ataxia, affecting 1 in 40,000 people globally. FRDA is caused by a mutation that reduces expression of the mitochondrial protein Frataxin (FXN). While there have been significant advances in understanding the cellular roles of FXN, many questions remain, especially concerning its roles during early development. Here, we developed a zebrafish loss of function model to study the role of Fxn during early embryogenesis. fxn-deficient zebrafish exhibited failure to thrive, edema, elevated cell death in the central nervous system, craniofacial defects, as well as stunted renal development and reduced kidney function that was associated with alterations in nephron lineage formation. Our findings reveal that Fxn is crucial for the normal development of multiple embryonic tissues, and disclose for the first time that Fxn plays important roles in supporting the pattern formation of the embryonic kidney. This Fxn loss of function model provides a new platform for future research to further expand our understanding about the roles of Fxn during ontogeny. 1. Introduction Friedreich's Ataxia (FRDA, OMIM #229300) is an autosomal recessive neurodegenerative disease and the most common inheritable ataxia (Anheim et al., 2010; 2012;Puccio et al., 2014). FRDA is caused by genetic mutations that reduce expression of the protein Frataxin (FXN). The vast majority (96-98%) of patients have variable numbers of trinucleotide GAA repeats in the first intron of the FXN gene, though genetic lesions encoding other mutations have also been identified (