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