Fig. 8. A schematic model of MIS actions at the early stage of Müllerian duct regression. Müllerian duct (M) formation and initial MISRII expression (dark blue) in the coelomic epithelium (gray) are similar in male and female urogenital ridges at E13 and early E14. After E14.5, MIS signaling (yellow) becomes functional in the male, driving the MISRII-expressing cells into the area adjacent to the Müllerian duct and eventually around the Müllerian duct at E15.5. This is an epithelial-to-mesenchymal transition. Meanwhile, MIS also upregulates ALK2 and SMAD8 and downregulates SMAD5. These combined activities have roles in Müllerian duct regression, as noted by the smaller Müllerian duct after E15.5, which disappears eventually. At this time, ALK3 and SMAD8, which are highly expressed in the Müllerian duct mesenchyme may mediate MIS signaling and Müllerian duct regression. Expression of MISRII remains in the coelomic epithelium of female urogenital ridges during this period. M, Müllerian duct; W, Wolffian duct.