High-Throughput Sequencing Analyses of XX Genital Ridges Lacking FOXL2 Reveal DMRT1 Up-Regulation Before SOX9 Expression During the Sex-Reversal Process in Goats
High-Throughput Sequencing Analyses of XX Genital Ridges Lacking FOXL2 Reveal DMRT1 Up-Regulation Before SOX9 Expression During the Sex-Reversal Process in Goats
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DOI：
10.1095/biolreprod.114.122796
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发表时间：
2014-12-01
影响因子：
3.6
通讯作者：
Pannetier, Maelle
中科院分区：
文献类型：
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作者：
Elzaiat, Maeva;Jouneau, Luc;Pannetier, Maelle
山羊FOXL2功能的丧失导致卵巢向睾丸的早期转分化，然后导致XX纯合突变体的完全性逆转。相比之下，小鼠中Foxl2功能的丧失诱导出生后卵泡形成的停滞，随后是完全的雌性不育。为了了解FOXL2在山羊卵巢分化过程中的分子作用，通过比较表达FOXL2蛋白或不表达FOXL2蛋白的XX性腺的mRNA谱，在性腺性别特异性分化的最早阶段确定推定的FOXL2靶基因。在这163个去调控的基因中，大约三分之二对应于FOXL2缺失时上调的睾丸基因，只有19个代表女性相关基因，在FOXL2缺失时下调。因此，FOXL2应该被视为一个抗睾丸基因，而不是作为一个女性促进基因。特别是，关键的睾丸决定基因DMRT 1被发现在SOX 9之前上调，因此表明在山羊中SOX 9的主要上调可能需要DMRT 1。总的来说，我们的研究结果等同于FOXL2是一个抗睾丸基因，使我们能够提出一个替代模型的性别决定过程中的山羊，略有不同，从小鼠中证明。
FOXL2 loss of function in goats leads to the early trans-differentiation of ovaries into testes, then to the full sex reversal of XX homozygous mutants. By contrast, Foxl2 loss of function in mice induces an arrest of follicle formation after birth, followed by complete female sterility. In order to understand the molecular role of FOXL2 during ovarian differentiation in the goat species, putative FOXL2 target genes were determined at the earliest stage of gonadal sex-specific differentiation by comparing the mRNA profiles of XX gonads expressing the FOXL2 protein or not. Of these 163 deregulated genes, around two-thirds corresponded to testicular genes that were up-regulated when FOXL2 was absent, and only 19 represented female-associated genes, down-regulated in the absence of FOXL2. FOXL2 should therefore be viewed as an antitestis gene rather than as a female-promoting gene. In particular, the key testis-determining gene DMRT1 was found to be up-regulated ahead of SOX9, thus suggesting in goats that SOX9 primary up-regulation may require DMRT1. Overall, our results equated to FOXL2 being an antitestis gene, allowing us to propose an alternative model for the sex-determination process in goats that differs slightly from that demonstrated in mice.