Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA.
Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA 94143, USA.
Development. 2022 May 15;149(10). doi: 10.1242/dev.200181. Epub 2022 May 26.
Tissue fusion frequently requires the removal of an epithelium that intervenes distinct primordia to form one continuous structure. In the mammalian secondary palate, a midline epithelial seam (MES) forms between two palatal shelves and must be removed to allow mesenchymal confluence. Abundant apoptosis and cell extrusion support their importance in MES removal. However, genetically disrupting the intrinsic apoptotic regulators BAX and BAK within the MES results in complete loss of cell death and cell extrusion, but successful removal of the MES. Novel static- and live-imaging approaches reveal that the MES is removed through streaming migration of epithelial trails and islands to reach the oral and nasal epithelial surfaces. Epithelial trail cells that express the basal epithelial marker ΔNp63 begin to express periderm markers, suggesting that migration is concomitant with differentiation. Live imaging reveals anisotropic actomyosin contractility within epithelial trails, and genetic ablation of actomyosin contractility results in dispersion of epithelial collectives and failure of normal MES migration. These findings demonstrate redundancy between cellular mechanisms of morphogenesis, and reveal a crucial and unique form of collective epithelial migration during tissue fusion.
组织融合通常需要去除介入不同原基以形成一个连续结构的上皮。在哺乳动物的次级腭中，中线上皮缝（MES）在两个腭突之间形成，必须去除以允许间质融合。大量的细胞凋亡和细胞外排支持它们在 MES 去除中的重要性。然而，在 MES 中遗传破坏内在凋亡调节剂 BAX 和 BAK 会导致细胞死亡和细胞外排完全丧失，但 MES 仍能成功去除。新的静态和实时成像方法揭示，MES 通过上皮轨迹和岛屿的流动迁移到达口腔和鼻腔上皮表面来去除。表达基底上皮标记物 ΔNp63 的上皮轨迹细胞开始表达外皮标记物，表明迁移伴随着分化。实时成像揭示了上皮轨迹中的各向异性肌动球蛋白收缩性，肌动球蛋白收缩性的遗传消融导致上皮集体的分散和正常 MES 迁移的失败。这些发现表明形态发生的细胞机制之间存在冗余性，并揭示了组织融合过程中集体上皮迁移的一种关键而独特的形式。
