Regulatory back-up circuit of medaka Wt1 co-orthologs ensures PGC maintenance.

In mammals, the Wilms' tumor suppressor gene, Wt1, encodes a transcription factor critical for development of the urogenital system. In teleost fish, however, two wt1 genes have been identified. In medaka wt1a is expressed in the lateral plate mesoderm during early embryogenesis. Later in development, wt1a is additionally expressed in the somatic cells of the gonadal primordium. We show here for the first time that in teleosts wt1 gene expression is observed during gonad development. Wt1b is expressed later during embryogenesis and is not expressed in the gonadal primordium. Analysis of morpholino knockdown experiments revealed functions of wt1 genes in pronephros development. Unexpectedly, by down-regulating Wt1a protein we observed wt1b expression during embryogenesis in the wildtype wt1a expression domains including somatic cells of the gonadal primordium. Interestingly, neither wt1a nor wt1b morphants showed effects on the gonad development, whereas the double knockdown of wt1a and wt1b displayed strong influences on the number of primordial germ cell (PGC) during gonad development. Our results indicate that medaka wt1 co-orthologs show genetic redundancy in PGC maintenance or survival through responsive backup circuits. This provides first evidence for a conditional co-regulation of these genes within a transcriptional network.