[S1E14] Regulate [TOP]

The AMH signaling pathway shares type 1 receptors, ACVRI and BMPR1A, and downstream SMADs with the BMP pathway. This suggests that AMH-induced expression of Osx in the reproductive tract may be regulated by similar mechanisms as its regulation by BMP signaling in bone and tooth differentiation. During osteoblast differentiation, BMP signaling induces Osx expression by activation of Runx2 and also via independent mechanisms (32). In our study, Runx2 transcript is not differentially expressed between male and female E14.5 MD mesenchyme, suggesting in male reproductive tract differentiation Osx expression is independent of Runx2. In addition to BMP signaling, activated β-CATENIN up-regulates Osx expression in osteoblasts, cementoblasts, and long bones (21, 22). In our previous study, we found that β-catenin in the MD mesenchyme is required for AMH-induced regression of the MD. Intriguingly, we found that OSX protein was expressed in β-catenin conditional knockout male mesonephroi but Osx transcript levels were significantly reduced compared with controls. Because β-catenin conditional knockout mice have complete retention of the MD and Osx-null males only show a delay in MD regression, we interpret this to mean that Ctnnb1 is upstream of Osx but that there are other transcriptional activation inputs. Of note, the chromosomal location of the Osx gene is within 88 kb of the Amhr2 gene, and this linkage is conserved in mammals. This implies the potential for shared enhancer/regulatory elements for MD mesenchyme expression.

[S1E14] Regulate

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Interestingly, Park et al. (12) performed a related study but used microarrays to determine transcript profiles of whole E14.5 mesonephroi from wild-type and Amhr2 mutant males to identify AMH-induced genes. Our study (MD mesenchymal cells only) and the Park study (whole mesonephroi) resulted in very similar lists of genes up-regulated in male MD (12). This suggests gene activation that mediates MD regression is primarily occurring in the MD mesenchyme. 041b061a72