Department of Biology, Centre for Biomedical Research, University of Victoria, Victoria, British Columbia, Canada.
BMC Genomics. 2011 Jan 13;12:31. doi: 10.1186/1471-2164-12-31.
The products of cyp19, dax, foxl2, mis, sf1 and sox9 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.
Bacterial artificial chromosomes containing salmon dax1 and dax2, foxl2b and mis were isolated and the regulatory regions that control their expression were characterized. Transposon integrations are implicated in the shaping of the dax and foxl2 loci. Splice variants for cyp19b1 and mis in both embryonic and adult tissues were detected and characterized. We found that cyp19b1 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 mis 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 cyp19a and cyp19b1 are exerted, despite transcription of their transactivators (ie; dax1, foxl2, sf1) occurring much earlier during embryonic development.
We report the embryonic and extragonadal expression of dax, foxl2, mis and other differentiation factors that indicate that they have functions that are more general and not restricted to steroidogenesis and gonadogenesis. Spliced cyp19b1 and mis transcripts are generated that may provide regulatory controls for tissue- or development-specific activities. Selection of cyp19b1 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 dax1 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.
cyp19、dax、foxl2、mis、sf1 和 sox9 的产物都与脊椎动物的性别决定过程有关。我们提供了鲑鱼发育早期以及下丘脑-垂体-肾上腺/性腺（HPAG）轴外组织中这些调节剂表达的证据。尽管这些因素在性别分化中的功能已经确定，但它们在性命运决定之前的早期发育中和大脑或性腺以外的组织中的作用基本上是未知的。
分离了含有鲑鱼 dax1 和 dax2、foxl2b 和 mis 的细菌人工染色体，并对其表达的调控区进行了表征。转座子整合与 dax 和 foxl2 基因座的形成有关。在胚胎和成年组织中检测到并表征了 cyp19b1 和 mis 的剪接变体。我们发现，由于内含子 1 的 3'端的隐蔽剪接，产生了含有不同长度 5'非翻译区的 cyp19b1 转录本。我们还证明，鲑鱼 mis 转录本可以编码具有不同 C 末端并在 MIS 激素翻译之前终止的前导肽产物。尽管其转录激活物（即 dax1、foxl2、sf1）在胚胎发育早期更早发生，但两种不同的芳香酶 cyp19a 和 cyp19b1 的表达存在调节差异。
我们报告了 dax、foxl2、mis 和其他分化因子的胚胎和性腺外表达，这表明它们具有更普遍的功能，而不仅仅局限于类固醇生成和性腺发生。产生的剪接 cyp19b1 和 mis 转录本可能为组织或发育特异性活性提供调节控制。cyp19b1 转录本的选择可能受到 DAX-1、FOXL2 和 SF-1 复合物的调节，这些复合物结合内含子 1 中的基序，或者受到招募剪接因子的外显子 2 内的信号的调节，或者两者兼而有之。仅携带 MIS 前导肽 N 端的蛋白质的翻译可能会调节其他 TGF β 家族成员在不同组织中的功能。dax1 在鲑鱼胚胎发生中的早期表达暗示了它作为谱系决定因子的作用。讨论了这些因子在胚胎发生中和 HPAG 轴外的其他作用。
