Analysis of the distal urinary tract in larval and adult zebrafish reveals homology to the human system.

Little is known about the distal excretory component of the urinary tract in Danio rerio (zebrafish). This component is affected by many human diseases and disorders of development. Here, we undertook multi-level analyses to determine the structure and composition of the distal urinary tract in the zebrafish. In silico searches identified uroplakin 1a, 2-like and 3-like genes in the zebrafish genome (orthologues to genes that encode urothelium-specific proteins in humans). In situ hybridization demonstrated uroplakin-1a expression in the zebrafish pronephros and cloaca from 96 hours post-fertilisation. H&E sectioning of adult zebrafish demonstrated two mesonephric ducts uniting into a urinary bladder which leads to a distinct urethral opening. Immunohistochemistry identified Uroplakin 1a and 2 expression and Gata3 expression in zebrafish urinary bladder cell layers that match human urothelial expression. Fluorescent dye injections demonstrated zebrafish urinary bladder function, including urine storage, intermittent micturition, and a urethral orifice separate from the larger anal canal and rectum. Our findings reveal homology between the urinary tracts of zebrafish and humans and offer the former as a model system to study disease.