Although implicated in adhesion, only a few studies address how the actin assembly factors guide cell positioning in multicellular tissues. The formin, Dia1, localizes to the proliferative basal layer of the epidermis. In organotypic cultures, Dia1 depletion reduced basal cell density and resulted in stratified tissues with disorganized differentiation and proliferative markers. Since crowding induces differentiation in epidermal tissues, we hypothesized that Dia1 is essential to reach densities amenable to differentiation before or during stratification. Consistent with this, forced crowding of Dia1-deficient cells rescued transcriptional abnormalities. We find Dia1 promotes rapid growth of lateral cell–cell adhesions, necessary for the construction of a highly crowded monolayer. In aggregation assays, cells sorted into distinct layers based on Dia1 expression status. These results suggest that as basal cells proliferate, reintegration and packing of Dia1-positive daughter cells is favored, whereas Dia1-negative cells tend to delaminate to a suprabasal compartment. This work elucidates the role of formin expression patterns in constructing distinct cellular domains within stratified epithelia.

中文翻译：

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Dia1 协调复层上皮的分化和细胞分选

尽管与粘附有关，但只有少数研究涉及肌动蛋白组装因子如何指导多细胞组织中的细胞定位。福明 (Dia1) 定位于表皮的增殖基底层。在器官型培养物中，Dia1 缺失会降低基底细胞密度，并导致分层组织的分化和增殖标记紊乱。由于拥挤会诱导表皮组织分化，我们假设 Dia1 对于在分层之前或分层过程中达到适合分化的密度至关重要。与此相一致的是，强制拥挤 Dia1 缺陷细胞可以挽救转录异常。我们发现 Dia1 促进横向细胞间粘附的快速生长，这对于构建高度拥挤的单层是必需的。在聚集测定中，细胞根据 Dia1 表达状态分为不同的层。这些结果表明，随着基底细胞增殖，有利于 Dia1 阳性子细胞的重新整合和包装，而 Dia1 阴性细胞倾向于分层至基底上隔室。这项工作阐明了福尔明表达模式在构建复层上皮内不同细胞结构域中的作用。