Project Summary
Disorders of sexual development (DSDs) encompass a variety of congenital conditions that present with
diverse phenotypes, such as virilization, gonadal dysgenesis, and delayed or absent puberty. In addition,
affected individuals often suffer from secondary effects, including gender dysphoria and physical issues such as
germ cell tumors and fertility disorders like polycystic ovarian syndrome or azoospermia. DSDs are the result of
genetic, developmental, or hormonal anomalies that arise during embryogenesis and persist throughout sexual
development and into adulthood. To better understand the etiology of DSDs, the role of RNA binding proteins in
sex determination has been investigated due to their functions in controlling gene expression via post-
transcriptional splicing, translational control, and mRNA localization. Identifying RNA binding protein RNA targets
and characterizing these regulatory relationships is essential to further our understanding of mechanisms
regulating sex determination. To study the events of sex determination and differentiation, our laboratory uses
zebrafish, a genetically tractable model with high fecundity and rapid external development. Therefore, this
powerful vertebrate system allows characterization of factors and pathways that are essential to reproductive
development, successful fertility, and establishment and maintenance of the female gonad. The aims herein will
identify conserved genes and mechanisms, that when disrupted, contribute to DSDs, fertility disorders, and
cancers in humans. Specifically, the aims of this proposal will investigate the factors and mechanisms regulating
sex-specific determination and differentiation in the context of a conserved vertebrate specific RNA binding
protein and its targets. Further, completion of these aims will provide rigorous training in all aspects of genetic
and molecular-based analyses, including generation, characterization, and validation of mutant and transgenic
zebrafish lines, genomic cloning, and microscopy, which will foster my development as a successful independent
investigator in the fields of developmental and reproductive biology.