Akt-dependent Pp2a activity is required for epidermal barrier formation during late embryonic development

Area of Science:

• Developmental Biology
• Molecular Biology
• Dermatology

Background:

• Epidermal barrier function is essential for protecting the fetus from the external environment.
• Barrier acquisition in mice occurs late in gestation, preceding birth.
• Understanding the molecular mechanisms of epidermal barrier formation is critical for developmental research.

Purpose of the Study:

• To investigate the molecular pathways involved in epidermal barrier formation during late mouse gestation.
• To elucidate the roles of Akt signaling and protein phosphatase 2A (Pp2a) in this process.
• To identify key regulatory subunits of Pp2a involved in epidermal development.

Main Methods:

• Utilized embryonic explant experiments with inhibitor treatments targeting Akt and Pp2a signaling.
• Employed siRNA-mediated knockdown of Ppp2r2a (a regulatory subunit of Pp2a).
• Assessed epidermal barrier function and Jun phosphorylation levels in response to molecular manipulations.

Main Results:

• Akt signaling and Jun dephosphorylation increased during epidermal barrier acquisition.
• Inhibition of Akt or Pp2a signaling disrupted epidermal barrier formation.
• Knockdown of Ppp2r2a led to increased Jun phosphorylation and impaired barrier acquisition.
• Restoration of barrier function was achieved by inhibiting Jun phosphorylation.

Conclusions:

• A novel Akt-dependent Pp2a pathway regulates Jun dephosphorylation, which is essential for embryonic epidermal barrier formation.
• Ppp2r2a acts as a crucial regulatory subunit of Pp2a, targeting it to Jun.
• This pathway represents a key mechanism for initial barrier formation during late embryonic development.