Müllerian duct maintenance at the cranial region is promoted by Gata2

Abstract

The paradigm of sexual differentiation holds that female embryos retain Mullerian ducts (the precursor to female reproductive tract) by default in the absence of anti-Mullerian hormone (AMH). However, whether Mullerian duct maintenance requires active signaling has remained unclear. Here, we discover that the deletion of mesenchymal Gata2 induces selective regression of the cranial Mullerian duct (future oviduct). This regression is not driven by ectopic AMH signaling, but rather by the loss of region-specific NRG1 signaling. In contrast, the caudal Mullerian duct (future uterus) is retained and displays disrupted epithelial differentiation upon Gata2 deletion in either the mesenchymal or epithelial compartments. Our findings reveal a region-specific, GATA2-dependent program that actively maintains the cranial Mullerian duct, reshaping our understanding of female reproductive tract development.