Jia, S.; Fogarty, A.; Bai, W.; Zhao, F.

The paradigm of sexual differentiation holds that female embryos retain M&uumlllerian ducts (the precursor to female reproductive tract) by default in the absence of anti-M&uumlllerian hormone (AMH). However, whether M&uumlllerian duct maintenance requires active signaling has remained unclear. Here, we discover that the deletion of mesenchymal Gata2 induces selective regression of the cranial M&uumlllerian 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 M&uumlllerian 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 M&uumlllerian duct, reshaping our understanding of female reproductive tract development.