Sreenivasan, R., Jiang, J., Wang, X., Bartfai, R., Kwan, H.Y., Christoffels, A., and Orban, L. (2014) Gonad Differentiation in Zebrafish Is Regulated by the Canonical Wnt Signaling Pathway. Biology of reproduction. 90(2):45.
Zebrafish males undergo a 'juvenile ovary-to-testis' type gonadal transformation process. Several genes, including nuclear receptor subfamily 5, group A genes (nr5a) and anti-Mullerian hormone (amh), and pathways such as Tp53-mediated germ-cell apoptosis have been implicated in zebrafish testis formation. However, our
knowledge on the regulation of this complex process is incomplete and much remains to be understood about the molecular pathways
and network of genes that control it. Through a microarray-based analysis of transforming zebrafish male gonads, we demonstrated
that their transcriptomes undergo a transition from an ovary-like pattern through to an ovotestis to an adult testis-like
profile. The microarray results also validated previous histological and immunohistochemical observations that there is a
high variation in the duration and extent of commitment to the juvenile ovary phase among individuals. Interestingly, global
gene expression profiling of diverging zebrafish juvenile ovaries and transforming ovotestes revealed that some members of
the canonical Wnt/beta-catenin signaling pathway were differentially expressed between these two phases. To investigate if
Wnt/beta-catenin signaling plays a role in zebrafish gonad differentiation, we used the Tg(hsp70l:dkk1b-GFP)w32 line to inhibit Wnt/beta-catenin signaling during gonad differentiation. Activation of dkk1b-GFP expression by heat shock resulted in an increased proportion of males with corresponding decrease in gonadal aromatase gene
(cyp19a1a) expression. The Wnt target gene, lymphocyte enhancer binding factor 1 (lef1), was also down-regulated in the process. Together, these results provide the first functional evidence that, similarly to
mammals, Wnt/beta-catenin signaling is a "pro-female" pathway that regulates gonad differentiation in zebrafish.