| Summary: | Background: The products of cyp19, dax, foxl2, mis, sf1 and sox9 have each been associated with sex-determiningprocesses among vertebrates. We provide evidence for expression of these regulators very early in salmoniddevelopment and in tissues outside of the hypothalamic-pituitary-adrenal/gonadal (HPAG) axis. Although thefunction of these factors in sexual differentiation have been defined, their roles in early development before sexualfate decisions and in tissues beyond the brain or gonad are essentially unknown.Results: Bacterial artificial chromosomes containing salmon dax1 and dax2, foxl2b and mis were isolated and theregulatory regions that control their expression were characterized. Transposon integrations are implicated in theshaping of the dax and foxl2 loci. Splice variants for cyp19b1 and mis in both embryonic and adult tissues weredetected and characterized. We found that cyp19b1 transcripts are generated that contain 5’-untranslated regionsof different lengths due to cryptic splicing of the 3’-end of intron 1. We also demonstrate that salmon mistranscripts can encode prodomain products that present different C-termini and terminate before translation of theMIS hormone. Regulatory differences in the expression of two distinct aromatases cyp19a and cyp19b1 are exerted,despite transcription of their transactivators (ie; dax1, foxl2, sf1) occurring much earlier during embryonicdevelopment.Conclusions: We report the embryonic and extragonadal expression of dax, foxl2, mis and other differentiationfactors that indicate that they have functions that are more general and not restricted to steroidogenesis andgonadogenesis. Spliced cyp19b1 and mis transcripts are generated that may provide regulatory controls for tissueordevelopment-specific activities. Selection of cyp19b1 transcripts may be regulated by DAX-1, FOXL2 and SF-1complexes that bind motifs in intron 1, or by signals within exon 2 that recruit splicing factors, or both. Thepotential translation of proteins bearing only the N-terminal MIS prodomain may modulate the functions of otherTGF b family members in different tissues. The expression patterns of dax1 early in salmon embryogenesisimplicate its role as a lineage determination factor. Other roles for these factors during embryogenesis and outsidethe HPAG axis are discussed.
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