Basement membrane remodelling regulates mouse embryogenesis
Basement membrane remodelling regulates mouse embryogenesis
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DOI：
10.1038/s41586-020-2264-2
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发表时间：
2020-06-11
期刊：
影响因子：
64.8
通讯作者：
Zernicka-Goetz, Magdalena
中科院分区：
文献类型：
--
作者：
Kyprianou, Christos;Christodoulou, Neophytos;Zernicka-Goetz, Magdalena
发育过程中的组织雕刻主要归因于细胞事件，如会聚延伸或根尖收缩（1,2）。然而，最近的研究揭示了基底膜重塑在整体组织形态发生中的作用（3-5）。着床后，小鼠胚胎的外胚层和外胚层被基膜包裹。基底膜和这些组织之间的信号传导对于细胞极化和随后的形态发生至关重要（6,7）。然而，基底膜在着床后胚胎发生中的机械作用尚不清楚。在这里，我们证明了时空调节基底膜重构在早期胚胎发育中的重要性。具体来说，我们表明节点信号通过调节基质金属蛋白酶的表达来指导基底膜穿孔的产生和动态分布。这种基底膜的重塑有助于胚胎在原肠形成前的生长。前后轴的建立（8,9）进一步调节基底膜重构，通过定位结节信号，从而调控基质金属蛋白酶的活性和基底膜穿孔，使其位于胚胎的后侧。在原肠胚形成过程中，后侧的穿孔对于原始条纹的延伸是必不可少的，因为它使未来原始条纹的基底膜更容易破裂。因此，时空调节的基底膜重构有助于胚胎生长、形态发生和原肠形成的协调。
Tissue sculpting during development has been attributed mainly to cellular events through processes such as convergent extension or apical constriction(1,2.) However, recent work has revealed roles for basement membrane remodelling in global tissue morphogenesis(3-5). Upon implantation, the epiblast and extraembryonic ectoderm of the mouse embryo become enveloped by a basement membrane. Signalling between the basement membrane and these tissues is critical for cell polarization and the ensuing morphogenesis(6,7). However, the mechanical role of the basement membrane in post-implantation embryogenesis remains unknown. Here we demonstrate the importance of spatiotemporally regulated basement membrane remodelling during early embryonic development. Specifically, we show that Nodal signalling directs the generation and dynamic distribution of perforations in the basement membrane by regulating the expression of matrix metalloproteinases. This basement membrane remodelling facilitates embryo growth before gastrulation. The establishment of the anterior-posterior axis(8,9) further regulates basement membrane remodelling by localizing Nodal signalling-and therefore the activity of matrix metalloproteinases and basement membrane perforations-to the posterior side of the embryo. Perforations on the posterior side are essential for primitive-streak extension during gastrulation by rendering the basement membrane of the prospective primitive streak more prone to breaching. Thus spatiotemporally regulated basement membrane remodelling contributes to the coordination of embryo growth, morphogenesis and gastrulation.