Epithelial invagination by vertical telescoping
Epithelial invagination by vertical telescoping
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垂直伸缩导致上皮内陷
DOI：
10.1101/515981
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Li J
上皮弯曲是器官发育过程中塑造器官的一个基本过程。目前已知的所有机制都涉及细胞局部从柱状改变为楔形。这种形状的改变通常是通过细胞顶端的细胞骨架收缩(“顶端收缩”)发生的，但也知道诸如基底核定位(“基底部楔形”)或外在压缩的机制。在这里，我们演示了一种完全不同的机制，它发生在没有细胞楔形的情况下。在哺乳动物的唾液腺和牙齿中，我们发现最初的内陷是通过协调的垂直细胞运动发生的。具体地说，我们展示了位于胎盘边缘的细胞垂直向上移动，而它们更中心的邻居则向下移动，以产生内陷。我们进一步证明，这是通过活跃的细胞间迁移发生的：外部细胞迁移，顶端前沿突起，压低中央细胞，将上皮向下伸展到下面的间质中。细胞基本附着在下层椎板上，而它们的根尖突起是动态的，向心地呈平面极化。这些突起依赖于肌动蛋白细胞骨架，抑制分支分子Arp2/3就会抑制它们和内陷。成纤维细胞生长因子和刺猬形态原信号也是必需的，成纤维细胞生长因子提供了方向提示。这些发现表明，上皮弯曲可以通过与先前认识的内陷过程完全不同的协调细胞重排的新的形态发生机制来实现。
Epithelial bending is a fundamental process that shapes organs during development. All currently known mechanisms involve cells locally changing shape from columnar to wedge-shaped. Often this shape change occurs by cytoskeletal contraction at cell apices (“apical constriction”) but mechanisms such as basal nuclear positioning (“basal wedging”) or extrinsic compression are also known. Here we demonstrate a completely different mechanism which occurs without cell wedging. In mammalian salivary glands and teeth, we show that initial invagination occurs through coordinated vertical cell movement. Specifically, we show that cells towards the periphery of the placode move vertically upwards while their more central neighbours move downwards to create the invagination. We further show that this occurs by active cell-on-cell migration: outer cells migrate with an apical leading edge protrusion, depressing the central cells to “telescope” the epithelium downwards into the underlaying mesenchyme. Cells remain basally attached to the underlying lamina while their apical protrusions are dynamic and planar polarised centripetally. These protrusions depend on the actin cytoskeleton, and inhibition of the branching molecule Arp2/3 inhibits them and the invagination. FGF and Hedgehog morphogen signals are also required, with FGF providing a directional cue. These findings show that epithelial bending can be achieved by novel morphogenetic mechanism of coordinated cell rearrangement quite distinct from previously recognised invagination processes.