Finding clues to the riddle of sex determination in zebrafish.

How sex is determined has been one of the most intriguing puzzles in biology since antiquity. Although a fundamental process in most metazoans, there seems to be myriad of ways in which sex can be determined - from genetic to environmental sex determination. This variation is limited mainly to upstream triggers with the core of sex determination pathway being conserved. Zebrafish has gained prominence as a vertebrate model system to study development and disease. However, very little is known about its primary sex determination mechanism. Here we review our current understanding of the sex determination in zebrafish. Zebrafish lack identifiable heteromorphic sex chromosomes and sex is determined by multiple genes, with some influence from the environment. Recently, chromosome 4 has been identified as sex chromosome along with few sex-linked loci on chromosomes 5 and 16. The identities of candidate sex-linked genes, however, have remained elusive. Sex in zebrafish is also influenced by the number of meiotic oocytes in the juvenile ovary, which appear to instruct retention of the ovarian fate. The mechanism and identity of this instructive signal remain unknown. We hypothesize that sex in zebrafish is a culmination of combinatorial effects of the genome, germ cells and the environment with inputs from epigenetic factors translating the biological meaning of this interaction.