Epiboly generates the epidermal basal monolayer and spreads the nascent mammalian skin to enclose the embryonic body.
Epiboly generates the epidermal basal monolayer and spreads the nascent mammalian skin to enclose the embryonic body.
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DOI：
10.1242/jcs.180703
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发表时间：
2016-05-01
影响因子：
4
通讯作者：
Formstone CJ
中科院分区：
文献类型：
--
作者：
Panousopoulou E;Hobbs C;Mason I;Green JB;Formstone CJ
表代谢是羊膜动物原肠胚形成过程中外胚层表面覆盖整个胚胎的一个形态发生过程。我们在这里提出，哺乳动物也利用这一过程来扩大表皮，并将体腔和脊髓包裹在一个保护性的表面上。我们的数据支持一个模型，即表皮扩张是由表皮基底层祖细胞单层的初步建立驱动的，通过径向细胞向基底层嵌入多层上皮。通过使用悬浮型培养策略，我们发现这个过程是纤维连接蛋白依赖的，并且对皮肤是自主的。驱动表皮扩张的放射状细胞重排也需要ROCK活性，但它是由细胞突起而不是肌球蛋白II收缩性驱动的。在Crash小鼠中，表皮前体细胞单层的形成和表皮扩张被延迟，这是由于其具有核心平面细胞极性（PCP）果蝇蛋白火烈鸟（也称为Stan）的同源基因Celsr1的显性突变。我们观察到Crash突变体腹壁封闭失败，这表明表皮扩散缺陷可能是腹壁出生缺陷的基础。初生哺乳动物表皮通过类似于表皮形成的过程向胚胎干周围扩散，这对人类腹壁出生缺陷具有重要意义。
Epiboly is a morphogenetic process that is employed in the surface ectoderm of anamniotes during gastrulation to cover the entire embryo. We propose here that mammals also utilise this process to expand the epidermis and enclose the body cavity and spinal cord with a protective surface covering. Our data supports a model whereby epidermal spreading is driven by the primary establishment of the epidermal basal progenitor monolayer through radial cell intercalation of a multi-layered epithelium towards the basal lamina. By using a suspension organotypic culture strategy, we find that this process is fibronectin-dependent and autonomous to the skin. The radial cell rearrangements that drive epidermal spreading also require ROCK activity but are driven by cell protrusions and not myosin II contractility. Epidermal progenitor monolayer formation and epidermal spreading are delayed in Crash mice, which possess a dominant mutation in Celsr1, an orthologue of the core planar cell polarity (PCP) Drosophila protein Flamingo (also known as Stan). We observe a failure of ventral enclosure in Crash mutants suggesting that defective epidermal spreading might underlie some ventral wall birth defects. Summary: The nascent mammalian epidermis spreads to enclose the embryo trunk through a process akin to epiboly, which has important implications for human birth defects of the abdominal wall.