期刊
DEVELOPMENT
卷 149, 期 10, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.200181
关键词
Palate; Collective cell migration; Apoptosis; Cell extrusion; Tgf beta; Cleft palate; Cleft lip; Craniofacial; Live imaging; Fusion; Actomyosin; Cell adhesion; Non-muscle myosin II; NMIIA; Mouse
资金
- National Institute of Dental and Craniofacial Research [R01DE025877, R35DE031926, F32DE030367]
- University of California
In tissue fusion, the removal of a midline epithelial seam (MES) is achieved through the migration of epithelial trails and islands, accompanied by cell differentiation and anisotropic actomyosin contractility. These findings demonstrate redundancy in cellular mechanisms of morphogenesis and reveal a unique form of collective epithelial migration during tissue fusion.
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 Delta Np63 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.
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