mTOR signaling regulates morphogenesis and differentiation during lacrimal gland development

Manabu Sakai1, Mahiro Murakami2, Takayoshi Sakai2

  • 1Department of Clinical Laboratory Science, The University of Tenri, 80-1 Bessyo, Tenri, Nara, 632-0018, Japan; Department of Oral-facial Disorders, Graduate School of Dentistry, The University of Osaka, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Insights

The mammalian target of rapamycin (mTOR) signaling pathway is crucial for lacrimal gland (LG) development. This study clarifies the roles of mTORC1, mTORC2, and AMPK in LG growth, both in organ cultures and in vivo.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Ophthalmology

Background:

  • Lacrimal gland (LG) development involves various molecules, but the role of the mammalian target of rapamycin (mTOR) signaling pathway, including mTORC1 and mTORC2, is not fully understood.
  • Investigating mTOR signaling dynamics is essential for understanding LG development mechanisms.

Purpose of the Study:

  • To elucidate the role of the mTOR signaling pathway, including mTORC1, mTORC2, and AMPK, in lacrimal gland development.
  • To investigate the effects of mTOR signaling inhibition on LG development in ex vivo organ cultures and in vivo mouse models.

Main Methods:

  • Utilized an ex vivo lacrimal gland (LG) organ culture system mimicking in vivo conditions.
  • Employed pharmacological inhibitors (rapamycin, LY294002, compound C) to study mTOR signaling dynamics.
  • Administered rapamycin to pregnant female ICR mice to assess in vivo effects on LG development.

Main Results:

  • Clarified that both mTORC1 and mTORC2 pathways via PI3K, and the mTOR signaling pathway via AMPK, are involved in LG development in ex vivo organ culture.
  • Observed decreased body weight and LG size in rapamycin-treated mice, indicating an in vivo role for mTOR signaling.
  • Demonstrated the involvement of mTOR signaling in regulating lacrimal gland growth.

Conclusions:

  • The mTOR signaling pathway, encompassing mTORC1, mTORC2, and AMPK, plays a significant role in lacrimal gland development.
  • Findings highlight the importance of mTOR signaling for both ex vivo and in vivo LG development.
  • This study provides novel insights into the molecular mechanisms governing lacrimal gland morphogenesis.

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