Fogarty, A. | bioRxiv Science

bioRxiv2026

M&uumlllerian duct maintenance at the cranial region is promoted by Gata2

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.

developmental biology↗

bioRxiv2025

Crucial roles of mesenchymal Gata2 in murine epididymal development

Androgens drive the morphogenesis and differentiation of the Wolffian duct (WD) into the epididymis, an essential organ for male reproduction, by binding to the androgen receptor (AR). However, it remains unclear whether other transcriptional programs operate beyond the central androgen/AR signaling in promoting WD development. We discovered that mesenchyme-specific deletion of the transcription factor Gata2 resulted in defective epididymal coiling in the corpus and caudal regions. The defective coiling in the absence of mesenchymal Gata2 did not result from androgen signaling deficiency, as there were no abnormalities in testicular morphology, androgen production, or AR/Ar expression, and dihydrotestosterone supplementation did not restore epididymal coiling in cultured WDs. Instead, Gata2 deletion reduced the expression of the mesenchyme- derived factor Inhba and epithelial proliferation, both of which play critical roles in epididymal coiling. The epididymal defect persisted into adulthood, with the uncoiled corpus and caudal epididymis exhibiting abnormal epithelial morphology and lumen environments, resulting in an unfavorable environment for sperm storage. Our results demonstrate the androgen-independent role of mesenchymal GATA2 in promoting epididymal development through Inhba induction and highlight the importance of proper fetal development in male reproduction. Significance StatementTesticular androgens drive the maintenance and differentiation of the Wolffian duct into a coiled and functional epididymis during male sexual differentiation. Our study, however, reveals that the Wolffian duct failed to develop into a coiled and functional epididymis in the absence of mesenchymal Gata2. This defect is not due to androgen signaling deficiency but rather to reduced expression of the mesenchyme-derived factor Inhba and decreased epithelial proliferation. Our results demonstrate the crucial role of GATA2-mediated transcriptional programs beyond the central androgen/androgen receptor signaling in Wolffian duct development.

developmental biology↗