GPR56: a novel gene essential for mullerian duct formation

Roly ZY, Major AT and Smith CA

Monash Biomedicine Institute, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria.

The embryonic Mullerian ducts give rise to the female reproductive tract. While a number of genes have been implicated in duct formation and differentiation, many of the molecular details remain obscure. In a recent RNA-seq analyses of the embryonic chicken urogenital system, we identified the adhesion-associated receptor, G-Protein coupled Receptor 56 (GPR56). We found the gene up-regulated in the Mullerian duct and developing ovary. GPR56 has not previously been liked to duct formation. Whole Mount in situ hybridisation confirmed GPR56 mRNA expression in the Mullerian Duct Epithelium (MDE) in both sexes during invagination and the elongation phases of duct formation. Collagen type III (COL3A1) is a putative ligand of GPR56. We found that COL3A1 is expressed in Mullerian Surface Epithelium (MSE) and Mullerian Duct Mesenchyme (MDM), but not in Mullerian Duct Epithelium (MDE). Thus, we hypothesise that GPR56 may interact with COL3A1 at the basal membrane junction between MDM and MDE of Mullerian Duct. Over expression of GPR56 had no overt effect upon duct development whereas targeted knockdown using RNAi perturbed the formation of Mullerian duct. Ducts were truncated and the expression of marker genes such as PAX2, was retarded or absent. We conclude that GPR56 is essential for the Mullerian duct formation and elongation. We hypothesise that GPR56 plays a role specifically in the duct epithelium during elongation through interaction with mesenchymal COL3A1. Keywords: GPR56, Adhesion G-protein-coupled receptors, Mullerian Duct, Chicken.