Figure 7.

The network of signaling pathways required for MD regression. The AMH canonical signaling pathway is shown in relation to the upstream and downstream Wnt canonical pathways that are required for MD regression. The canonical Wnt pathway on the right of the diagram shows how catenin is degraded in the absence of a Wnt signal. In the absence of Wnt signaling, TCF factors associate with Groucho family proteins to repress transcription (not shown). When Wnt binds to its receptors (Fz and LRP5/6), Disheveled (Dvl) is recruited and activated, resulting in the inhibition of the serine/threonine kinase, GSK-3, and leading to the accumulation of β-catenin and its translocation to the nucleus. In the nucleus, β-catenin displaces Groucho to bind TCF/LEF and activate transcription. Genes or proteins that affect MD regression as null mutations or conditional knockouts are indicated with red solid or dashed ovals, respectively. Genes that do not affect MD regression as null mutations or conditional knockouts are indicated with red solid or dashed rectangles, respectively. β-catenin is not circled in the Wnt7a pathway shown on the left because the conditional knockout of β-catenin did not affect expression of AMHR2. Since both Amhr2 and the Cre-recombinase (under the control of the Amhr2 promoter) would be induced at the same time, there is almost certainly a time delay between establishment of a competent AMH signaling pathway and the inactivation of β-catenin in the Wnt7a pathway required for the induction of AMHR2. Fz, Frizzled; LRP5/6, LDL-receptor-related protein 5/6; APC, adenomatous polyposis coli protein.