Death is the major fate of medial edge epithelial cells and the cause of basal lamina degradation during palatogenesis
Death is the major fate of medial edge epithelial cells and the cause of basal lamina degradation during palatogenesis
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DOI：
10.1242/dev.00907
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发表时间：
2004-01-01
期刊：
影响因子：
4.6
通讯作者：
Covarrubias, L
中科院分区：
文献类型：
--
作者：
Cuervo, R;Covarrubias, L
在哺乳动物发育过程中，一对搁板融合形成次级腭，这一过程需要每个搁板的内侧边缘上皮组织（medial edge epithelial tissue，METS）的粘附和所得内侧上皮缝（medial epithelial seam，MES）的变性。据报道，上皮间质转化（EMT）发生在货架融合，被认为是MES变性的基本过程。我们最近发现，细胞死亡是货架融合的必要过程。这些发现揭示了MES变性中细胞死亡的相关性;然而，它们并没有排除其他过程的参与。在目前的工作中，我们专注于评估的过程，可能有助于腭架融合。我们通过传统的染料标记的EMT细胞，通过感染携带lacZ基因的腺病毒的EMT细胞，并通过融合野生型货架与来自EGFP表达小鼠胚胎的货架来测试EMT。通过培养整个腭，或通过允许在融合过程中跟踪单个细胞的新型切片培养系统，跟踪标记细胞的命运。在间充质隔室中发现很少的标记细胞，并且几乎所有的标记细胞都经历细胞死亡。抑制金属蛋白酶可防止基膜降解，而不影响MES变性和胰岛细胞死亡。值得注意的是，独立于货架融合，细胞死亡的激活促进了基底层的降解（“细胞凋亡”）。最后，通过对牙周膜细胞（即覆盖基底上皮的浅表细胞）的特异性标记，我们观察到上皮接缝口端和鼻端的上皮三角形似乎不是由牙周膜细胞迁移引起的，而是由牙周膜细胞迁移引起的。抑制这些上皮细胞的迁移或去除表明它们具有控制上皮细胞粘附和存活的瞬时功能，并最终在上皮三角内死亡。我们的结论是，MES退化发生几乎唯一的细胞死亡，并为第一次，我们表明，这一过程可以激活在发展过程中的基膜降解。
During mammalian development, a pair of shelves fuses to form the secondary palate, a process that requires the adhesion of the medial edge epithelial tissue (MEE) of each shelf and the degeneration of the resulting medial epithelial seam (MES). It has been reported that epithelial-mesenchymal transformation (EMT) occurs during shelf fusion and is considered a fundamental process for MES degeneration. We recently found that cell death is a necessary process for shelf fusion. These findings uncovered the relevance of cell death in MES degeneration; however, they do not discard the participation of other processes. In the present work, we focus on the evaluation of the processes that could contribute to palate shelf fusion. We tested EMT by traditional labeling of MEE cells with a dye, by infection of MEE with an adenovirus carrying the lacZ gene, and by fusing wild-type shelves with the ones from EGFP-expressing mouse embryos. Fate of MEE labeled cells was followed by culturing whole palates, or by a novel slice culture system that allows individual cells to be followed during the fusion process. Very few labeled cells were found in the mesenchyme compartment, and almost all were undergoing cell death. Inhibition of metalloproteinases prevented basal lamina degradation without affecting MES degeneration and MEE cell death. Remarkably, independently of shelf fusion, activation of cell death promoted the degradation of the basal lamina underlying the MEE ('cataptosis'). Finally, by specific labeling of periderm cells (i.e. the superficial cells that cover the basal epithelium), we observed that epithelial triangles at oral and nasal ends of the epithelial seam do not appear to result from MEE cell migration but rather from periderm cell migration. Inhibition of migration or removal of these periderm cells suggests that they have a transient function controlling MEE cell adhesion and survival, and ultimately die within the epithelial triangles. We conclude that MES degeneration occurs almost uniquely by cell death, and for the first time we show that this process can activate basal lamina degradation during a developmental process.