Forces generated by cell intercalation tow epidermal sheets in mammalian tissue morphogenesis.

Area of Science:

• Developmental biology
• Cell biology
• Tissue engineering

Background:

• Gastrulation provides models for embryonic shaping, but later coordinated cell movements are less understood.
• Eyelid closure offers a model for localized epithelial reshaping, expansion, and movement over another epithelium.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms underlying embryonic eyelid closure.
• To differentiate eyelid closure from other developmental processes like wound repair and dorsal closure.

Main Methods:

• Live imaging, gene targeting, and cell-cycle inhibitors were used to analyze closure dynamics.
• Laser ablation and quantitative analysis of tissue deformations were employed to study force generation.
• In vivo functional analyses assessed the roles of specific molecular pathways.

Main Results:

• Eyelid closure does not require the overlying periderm, cell proliferation, or supracellular actin cables.
• Cell intercalation parallel to the tissue front locally compresses it, driving closure.
• The mechanism involves localized myosin-IIA, α5β1 integrin/fibronectin-mediated migration, and Wnt-stimulated E-cadherin downregulation.

Conclusions:

• Eyelid closure utilizes a unique mode of epithelial movement driven by cell intercalation.
• This process leverages internally generated forces to achieve tissue closure and expansion.
• The findings reveal a novel mechanism for epithelial sheet movement in later embryonic development.