Simulations of particle tracking in the oligociliated mouse node and implications for left-right symmetry breaking mechanics
Simulations of particle tracking in the oligociliated mouse node and implications for left-right symmetry breaking mechanics
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寡纤毛小鼠节点中的粒子跟踪模拟及其对左右对称破坏力学的影响
DOI：
10.1101/624940
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Gallagher M
中科院分区：
文献类型：
--
作者：
Gallagher M
内部解剖不对称的概念是熟悉的——通常在人类中，心脏在左边，肝脏在右边；然而，发育中的胚胎是如何知道产生这种一致的偏侧性的呢？对称性打破始于左右不对称纤毛驱动的流体力学，在一个小的充满液体的结构中，称为腹侧结。然而，是什么将这种流动转化为左右不对称发展的问题仍然没有答案。一个主要的假设是，血流在淋巴结内运输含有形态因子的囊泡，这些囊泡的吸收导致基因表达不对称。为了研究囊泡运输如何导致野生型和突变型实验中观察到的位置模式，我们扩展了开源的Stokes流包NEAREST，以考虑由1、2和112个跳动纤毛驱动的小鼠模型中颗粒的流体力学和布朗运动。本文模拟了三种含形态素颗粒在少纤毛和野生型小鼠胚胎中的释放模型：均匀随机释放、局部纤毛应力诱导释放和运动纤毛本身局部释放，以评估其与观察结果的相容性。只有均匀随机释放模型似乎与数据一致，局部释放模型都没有导致少毛胚中显著的转运。本文是西奥·墨菲会议议题“运动和运输中纤毛的统一性和多样性”的一部分。
The concept of internal anatomical asymmetry is familiar–usually in humans the heart is on the left and the liver is on the right; however, how does the developing embryo know to produce this consistent laterality? Symmetry-breaking initiates with left–right asymmetric cilia-driven fluid mechanics in a small fluid-filled structure called the ventral node in mice. However, the question of what converts this flow into left–right asymmetric development remains unanswered. A leading hypothesis is that flow transports morphogen-containing vesicles within the node, the absorption of which results in asymmetrical gene expression. To investigate how vesicle transport might result in the situs patterns observe in wild-type and mutant experiments, we extend the open-source Stokes flow package, NEAREST, to consider the hydrodynamic and Brownian motion of particles in a mouse model with flow driven by one, two and 112 beating cilia. Three models for morphogen-containing particle released are simulated to assess their compatibility with observed results in oligociliated and wild-type mouse embryos: uniformly random release, localized cilium stress-induced release and localized release from motile cilia themselves. Only the uniformly random release model appears consistent with the data, with neither localized release model resulting in significant transport in the oligociliated embryo.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
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影响因子：
6.4
作者：
Wang J;Barr MM
通讯作者：
Barr MM
壁应力增强了细胞外囊泡的胞吐作用，这是脊椎动物发育中左右对称性破坏的可能机制。
影响因子：
2
作者：
Solowiej-Wedderburn J
通讯作者：
Solowiej-Wedderburn J
影响因子：
9.8
作者：
Nonaka S;Yoshiba S;Watanabe D;Ikeuchi S;Goto T;Marshall WF;Hamada H
通讯作者：
Hamada H
DOI：
10.1126/science.1222538
发表时间：
2012-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yoshiba S;Shiratori H;Kuo IY;Kawasumi A;Shinohara K;Nonaka S;Asai Y;Sasaki G;Belo JA;Sasaki H;Nakai J;Dworniczak B;Ehrlich BE;Pennekamp P;Hamada H
通讯作者：
Hamada H
影响因子：
4.6
作者：
Kramer-Zucker, AG;Olale, F;Drummond, IA
通讯作者：
Drummond, IA