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  • Title: Hedgehog signaling regulates Wolffian duct development through the primary cilium†.
    Author: Alves MBR, Girardet L, Augière C, Moon KH, Lavoie-Ouellet C, Bernet A, Soulet D, Calvo E, Teves ME, Beauparlant CJ, Droit A, Bastien A, Robert C, Bok J, Hinton BT, Belleannée C.
    Journal: Biol Reprod; 2023 Feb 13; 108(2):241-257. PubMed ID: 36525341.
    Abstract:
    Primary cilia play pivotal roles in embryonic patterning and organogenesis through transduction of the Hedgehog signaling pathway (Hh). Although mutations in Hh morphogens impair the development of the gonads and trigger male infertility, the contribution of Hh and primary cilia in the development of male reproductive ductules, including the epididymis, remains unknown. From a Pax2Cre; IFT88fl/fl knock-out mouse model, we found that primary cilia deletion is associated with imbalanced Hh signaling and morphometric changes in the Wolffian duct (WD), the embryonic precursor of the epididymis. Similar effects were observed following pharmacological blockade of primary cilia formation and Hh modulation on WD organotypic cultures. The expression of genes involved in extracellular matrix, mesenchymal-epithelial transition, canonical Hh and WD development was significantly altered after treatments. Altogether, we identified the primary cilia-dependent Hh signaling as a master regulator of genes involved in WD development. This provides new insights regarding the etiology of sexual differentiation and male infertility issues.
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