Hindbrain neuropore tissue geometry determines asymmetric cell-mediated closure dynamics in mouse embryos.
Hindbrain neuropore tissue geometry determines asymmetric cell-mediated closure dynamics in mouse embryos.
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DOI：
10.1073/pnas.2023163118
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发表时间：
2021-05-11
影响因子：
11.1
通讯作者：
Galea GL
中科院分区：
文献类型：
--
作者：
Maniou E;Staddon MF;Marshall AR;Greene NDE;Copp AJ;Banerjee S;Galea GL
生物力学关闭发育中的大脑胚胎神经管失败会导致致命的无脑畸形。尽管它们的临床重要性，细胞力产生机制关闭神经管仍然知之甚少。这项跨学科的研究结合了形态计量学分析、小鼠胚胎实时成像和计算机建模，正式确定了完成中脑/后脑关闭的细胞行为。在这种情况下，确定了两种以前未被认识到的细胞力产生行为：间隙周围的超细胞肌动球蛋白钱包弦的收缩性和细胞向间隙的定向运动。这两种机制都是描述间隙闭合所必需的，它们产生的动力学实质上受到形态学施加的组织几何形状的影响。这项工作为中脑/后脑关闭的致命失败提供了一个广泛适用的生物物理框架。间隙闭合是一个常见的形态发生过程。在哺乳动物中，未能关闭胚胎后脑神经孔（HNP）间隙会导致致命的无脑畸形。我们观察到，小鼠HNP周围的表面外胚层细胞在其前缘组装了高张力的肌动球蛋白钱包线，并在胚胎中线建立了初始接触。纤维连接蛋白和层粘连蛋白存在，紧张素1在前缘的局灶粘连样点中积累。HNP间隙不对称地关闭，从其吻端比尾端更快，同时保持拉长的纵横比。基于细胞的物理模型确定了两种足以解释组织水平HNP闭合动力学的闭合机制：荷包弦收缩和通过主动爬行实现的定向细胞运动。结合这两种闭合机制加速了间隙闭合，并产生恒定速率的间隙缩短。包弦收缩减小，爬行增大间隙宽高比，两者的组合维持了间隙宽高比。闭合率不对称可以解释为胚胎组织几何形状不对称，即吻侧缺口尖端较窄，而激光消融推断的生物力学张力在缺口的吻侧和尾侧闭合点是等效的。在细胞水平上，物理模型预测，随着间隙缩短，HNP吻侧和尾侧极端的细胞会发生重排。这些行为可在小鼠胚胎中重现。因此，哺乳动物胚胎协调细胞和组织水平的力学来实现这个关键的间隙关闭事件。
Failure to biomechanically close the embryonic neural tube in the developing brain causes fatal anencephaly. Despite their clinical importance, which cellular force-generating mechanisms close the neural tube remains poorly understood. This interdisciplinary study combines morphometric analysis, mouse embryo live imaging, and in silico modeling to formally identify cellular behaviors which complete midbrain/hindbrain closure. Two cellular force-generating behaviors not previously appreciated to act in this context are identified: contractility of supracellular actomyosin purse strings around the gap and directional movement of cells toward the gap. Both these mechanisms are required to describe gap closure, and their resulting dynamics are substantially impacted by morphogenetically imposed tissue geometry. This work provides a broadly applicable biophysical framework underlying fatal failures of midbrain/hindbrain closure. Gap closure is a common morphogenetic process. In mammals, failure to close the embryonic hindbrain neuropore (HNP) gap causes fatal anencephaly. We observed that surface ectoderm cells surrounding the mouse HNP assemble high-tension actomyosin purse strings at their leading edge and establish the initial contacts across the embryonic midline. Fibronectin and laminin are present, and tensin 1 accumulates in focal adhesion-like puncta at this leading edge. The HNP gap closes asymmetrically, faster from its rostral than caudal end, while maintaining an elongated aspect ratio. Cell-based physical modeling identifies two closure mechanisms sufficient to account for tissue-level HNP closure dynamics: purse-string contraction and directional cell motion implemented through active crawling. Combining both closure mechanisms hastens gap closure and produces a constant rate of gap shortening. Purse-string contraction reduces, whereas crawling increases gap aspect ratio, and their combination maintains it. Closure rate asymmetry can be explained by asymmetric embryo tissue geometry, namely a narrower rostral gap apex, whereas biomechanical tension inferred from laser ablation is equivalent at the gaps’ rostral and caudal closure points. At the cellular level, the physical model predicts rearrangements of cells at the HNP rostral and caudal extremes as the gap shortens. These behaviors are reproducibly live imaged in mouse embryos. Thus, mammalian embryos coordinate cellular- and tissue-level mechanics to achieve this critical gap closure event.
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在哺乳动物组织形态发生中，细胞嵌入产生的力牵引表皮片。
影响因子：
11.8
作者：
Heller, Evan;Kumar, K. Vijay;Grill, Stephan W.;Fuchs, Elaine
通讯作者：
Fuchs, Elaine
影响因子：
2.4
作者：
Das D;Zalewski JK;Mohan S;Plageman TF;VanDemark AP;Hildebrand JD
通讯作者：
Hildebrand JD
影响因子：
19.6
作者：
Brugués A;Anon E;Conte V;Veldhuis JH;Gupta M;Colombelli J;Muñoz JJ;Brodland GW;Ladoux B;Trepat X
通讯作者：
Trepat X
DOI：
10.1073/pnas.1700934114
发表时间：
2017-06-27
影响因子：
11.1
作者：
Galea, Gabriel L.;Cho, Young-June;Copp, Andrew J.
通讯作者：
Copp, Andrew J.
影响因子：
11.8
作者：
Antoniades, Ioanna;Stylianou, Panayiota;Skourides, Paris A.
通讯作者：
Skourides, Paris A.