mTOR signaling regulates morphogenesis and differentiation during lacrimal gland development.

Various molecules are involved in the development of the lacrimal gland (LG), the role of the mammalian target of rapamycin (mTOR) signaling pathway, including mTORC1 and mTORC2, remains unclear. We first used an ex vivo LG organ culture system that closely mimics in vivo conditions to investigate the mTOR signaling-related proteins. To investigate the dynamics of mTOR signaling-related proteins during LG development, we employed an ex vivo LG organ culture system treated with pharmacological inhibitors, including rapamycin, LY294002, and compound C. In addition, to assess the involvement of mTOR signaling in vivo, rapamycin was administered to pregnant female ICR mice. In this study, we clarify for the first time that two pathways both mTORC1 and mTORC2 via PI3K, and mTOR signaling pathway via AMPK are related to LG development in ex vivo organ culture. In addition, we report that the rapamycin-treated mice exhibited decreased body weight and LG size. These findings suggest that the mTOR signaling pathway plays a crucial role in LG development both ex vivo and in vivo.