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Abstract：
Dlx5 and Dlx6 encode distal-less homeodomain transcription factors that are present in the genome as a linked pair at a single locus. Dlx5 and Dlx6 have redundant roles in craniofacial, skeletal, and uterine development. Previously, we performed a transcriptome comparison for anti-Müllerian hormone (AMH)-induced genes expressed in the Müllerian duct mesenchyme of male and female mouse embryos. In that study, we found that Dlx5 transcripts were nearly seven-fold higher in males compared to females and Dlx6 transcripts were found only in males, suggesting they may be AMH-induced genes. Therefore, we investigated the role of Dlx5 and Dlx6 during AMH-induced Müllerian duct regression. We found that Dlx5 was detected in the male Müllerian duct mesenchyme from E14.5 to E16.5. In contrast, in female embryos Dlx5 was detected in the Müllerian duct epithelium. Dlx6 expression in Müllerian duct mesenchyme was restricted to males. Dlx6 expression was not detected in female Müllerian duct mesenchyme or epithelium. Genetic experiments showed that AMH signaling is necessary for Dlx5 and Dlx6 expression. Müllerian duct regression was variable in Dlx5 homozygous mutant males at E16.5, ranging from regression like controls to a block in Müllerian duct regression. In E16.5 Dlx6 homozygous mutants, Müllerian duct tissue persisted primarily in the region adjacent to the testes. In Dlx5-6 double homozygous mutant males Müllerian duct regression was also found to be incomplete but more severe than either single mutant. These studies suggest that Dlx5 and Dlx6 act redundantly to mediate AMH-induced Müllerian duct regression during male differentiation.
摘要：
Dlx5和Dlx6编码作为在单个基因座处的连接对存在于基因组中的非远端同源域转录因子。Dlx5和Dlx6在颅面有多余的角色，骨骼，和子宫发育。以前,我们对雄性和雌性小鼠胚胎的苗勒管间质中表达的抗苗勒管激素（AMH）诱导的基因进行了转录组比较。在那项研究中,我们发现，与女性相比，男性的Dlx5转录本高出近7倍，而Dlx6转录本只在男性中发现，提示它们可能是AMH诱导的基因。因此,我们研究了Dlx5和Dlx6在AMH诱导的穆勒导管消退过程中的作用.我们发现在E14.5至E16.5的男性苗勒管间质中检测到Dlx5。相比之下,在雌性胚胎中,在穆勒管上皮中检测到Dlx5。Müllerian导管间质中的Dlx6表达仅限于男性。在女性苗勒管间质或上皮中未检测到Dlx6表达。遗传实验表明AMH信号传导是Dlx5和Dlx6表达所必需的。在E16.5的Dlx5纯合突变雄性中，Müllerian导管回归是可变的，从像对照的回归到Müllerian导管回归中的阻滞。在E16.5Dlx6纯合突变体中，苗勒管组织主要存在于睾丸附近的区域。在Dlx5-6双纯合突变体中，还发现Müllerian导管回归不完整，但比任何一个单突变体都严重。这些研究表明，Dlx5和Dlx6在男性分化过程中冗余地介导AMH诱导的穆勒导管消退。
