Correction of aberrant growth preserves tissue homeostasis

Area of Science:

• Developmental Biology
• Cell Biology
• Tissue Homeostasis

Background:

• Mutations occur frequently in healthy tissues, often leading to abnormal cellular behaviors like hyperproliferation.
• Despite mutations, tissues often remain phenotypically normal, but the mechanisms underlying this tolerance are unclear.

Purpose of the Study:

• To investigate how the adult skin epithelium maintains tissue architecture and homeostasis when challenged with mutant cells or deformations.
• To elucidate the cellular behaviors involved in the elimination or correction of aberrant tissue structures.

Main Methods:

• Intravital imaging was used to track the fate of mouse skin epithelium containing activated Wnt/β-catenin stem cells.
• The study analyzed the regression of growths and the role of wild-type cells in eliminating mutant cells.

Main Results:

• All growths deforming skin architecture underwent regression, regardless of size.
• Wild-type cells actively eliminated mutant cells through various cellular behaviors, dismantling aberrant structures.
• Post-regression, remaining structures were either eliminated or converted into functional skin appendages.
• The skin demonstrated plasticity by correcting oncogenic Hras-induced aberrancies and mutation-independent deformations.

Conclusions:

• The adult skin epithelium exhibits significant plasticity, tolerating both mutational and non-mutational insults.
• Dynamic cellular behaviors are crucial for restoring skin homeostasis after damage.
• This study reveals a conserved principle of tissue tolerance and repair in the skin.