Dia1 coordinates differentiation and cell sorting in a stratified epithelium.

Area of Science:

• Cell biology
• Developmental biology
• Tissue engineering

Background:

• Actin assembly factors are critical for cell positioning in tissues, but their specific roles remain understudied.
• The formin Dia1 is localized to the basal layer of the epidermis, suggesting a role in epidermal development.

Purpose of the Study:

• To investigate the function of Dia1 in epidermal cell positioning and tissue organization.
• To determine if Dia1 is essential for achieving cell densities required for proper epidermal differentiation and stratification.

Main Methods:

• Organotypic epidermal cultures were used to study the effects of Dia1 depletion.
• Cell density, differentiation markers, and proliferation were analyzed in Dia1-depleted and control tissues.
• Forced crowding experiments were performed on Dia1-deficient cells.
• Cell aggregation assays were utilized to assess cell sorting based on Dia1 expression.

Main Results:

• Dia1 depletion led to reduced basal cell density and disorganized differentiation and proliferation markers in stratified tissues.
• Forced crowding of Dia1-deficient cells rescued transcriptional abnormalities, supporting the hypothesis that Dia1 promotes density-dependent differentiation.
• Dia1 was found to promote rapid growth of lateral cell-cell adhesions, essential for forming a crowded monolayer.
• Cells sorted into distinct layers based on Dia1 expression in aggregation assays, with Dia1-positive cells reintegrating into basal layers and Dia1-negative cells delaminating.

Conclusions:

• Dia1 is essential for maintaining basal epidermal cell density and facilitating proper tissue stratification.
• Dia1 promotes cell-cell adhesion and packing, influencing cell positioning and the formation of distinct cellular domains within stratified epithelia.
• Understanding Dia1's role in cell positioning provides insights into the mechanisms governing tissue development and organization.