mTORC1 and mTORC2 regulate skin morphogenesis and epidermal barrier formation

Area of Science:

• Cellular biology
• Developmental biology
• Dermatology

Background:

• Mammalian target of rapamycin (mTOR) is a key regulator of cell growth and metabolism.
• The specific roles of mTOR signaling, particularly its complexes mTORC1 and mTORC2, in skin morphogenesis and epidermal development remain largely uncharacterized.

Purpose of the Study:

• To investigate the function of mTOR signaling in skin morphogenesis and epidermal development.
• To elucidate the distinct roles of mTORC1 and mTORC2 in these processes.

Main Methods:

• Epidermis-specific deletion of the Mtor gene in mice (mTOR^EKO).
• Analysis of skin phenotype, epidermal differentiation, and barrier formation in mutant mice.
• Epidermis-specific deletion of Raptor (mTORC1 component) and Rictor (mTORC2 component).

Main Results:

• Mice with epidermis-specific Mtor deletion (mTOR^EKO) exhibit severe skin defects, including impaired epidermal differentiation and lack of a protective barrier, leading to perinatal lethality.
• Loss of Raptor (mTORC1 component) in the epidermis recapitulates the phenotype observed in mTOR^EKO mutants.
• Epidermal deficiency of Rictor (mTORC2 component) results in hypoplastic epidermis and disrupted terminal differentiation, but these mice survive postnatally.

Conclusions:

• mTOR signaling plays a fundamental and essential role in skin morphogenesis and epidermal development.
• mTORC1 is critical for early epidermal differentiation and barrier formation, while mTORC2 influences late-stage terminal differentiation.
• Distinct functions of mTORC1 and mTORC2 regulate key aspects of epidermal development.