homeobox genes regulate Müllerian duct regression.

and encode distal-less homeodomain transcription factors that are present in the genome as a linked pair at a single locus. and 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 transcripts were nearly seven-fold higher in males compared to females and transcripts were found only in males, suggesting they may be AMH-induced genes. Therefore, we investigated the role of and during AMH-induced Müllerian duct regression. We found that was detected in the male Müllerian duct mesenchyme from E14.5 to E16.5. In contrast, in female embryos was detected in the Müllerian duct epithelium. expression in Müllerian duct mesenchyme was restricted to males. expression was not detected in female Müllerian duct mesenchyme or epithelium. Genetic experiments showed that AMH signaling is necessary for and expression. Müllerian duct regression was variable in homozygous mutant males at E16.5, ranging from regression like controls to a block in Müllerian duct regression. In E16.5 homozygous mutants, Müllerian duct tissue persisted primarily in the region adjacent to the testes. In double homozygous mutant males Müllerian duct regression was also found to be incomplete but more severe than either single mutant. These studies suggest that and act redundantly to mediate AMH-induced Müllerian duct regression during male differentiation.