Simulation of the nodal flow of mutant embryos with a small number of cilia: comparison of mechanosensing and vesicle transport hypotheses.
Simulation of the nodal flow of mutant embryos with a small number of cilia: comparison of mechanosensing and vesicle transport hypotheses.
复制标题
DOI：
10.1098/rsos.180601
复制
发表时间：
2018-08
影响因子：
3.5
通讯作者：
Ishikawa T
中科院分区：
文献类型：
--
作者：
Omori T;Winter K;Shinohara K;Hamada H;Ishikawa T
在脊椎动物胚胎中，身体平面上的左-右(L-R)不对称是由节流决定的。Shinohara等人。(Shinohara K等人)2012 NAT。交警。3622(DOI：10.1038/nComms1624))使用了DPCD和RFX3突变的小鼠胚胎，结果表明，只有少数纤毛足以实现L-R不对称。然而，这种微弱的纤毛血流破坏对称性的机制尚不清楚。与L-R不对称器官发生相关的流动信号尚未阐明，在发育生物学的研究领域中，两种不同的假说--囊泡运输和机械感觉--正处于争论之中。在这项研究中，我们开发了Shinohara等人报告的节点系统的计算模型。并用少量纤毛检验了这两个假设的可行性。旋转纤毛数量较少，局部诱导流动，结节内未观察到整体强流。只有当颗粒靠近纤毛时，颗粒才能有效地运输，颗粒的运输强烈依赖于纤毛的位置。纤毛位置对最大壁面切变率也有影响，但结周壁面平均切变率随纤毛数量的增加而单调增加。我们还研究了与机械转导调节有关的不动纤毛的膜张力。结果表明，当流体剪切速率为0.1 μN m−1时，底部仍能产生约0.1 N−1的张力，高压区也位于上游，下游出现负张力。这种定位可能有助于感觉周围的血流方向，因为时间平均的逆时针循环是通过几个纤毛的旋转在结节中诱导的。我们的数值结果支持机械传感假说，我们预计我们的研究将在不久的将来激发对机械转导的进一步实验研究。
Left–right (L-R) asymmetry in the body plan is determined by nodal flow in vertebrate embryos. Shinohara et al. (Shinohara K et al. 2012 Nat. Commun. 3, 622 (doi:10.1038/ncomms1624)) used Dpcd and Rfx3 mutant mouse embryos and showed that only a few cilia were sufficient to achieve L-R asymmetry. However, the mechanism underlying the breaking of symmetry by such weak ciliary flow is unclear. Flow-mediated signals associated with the L-R asymmetric organogenesis have not been clarified, and two different hypotheses—vesicle transport and mechanosensing—are now debated in the research field of developmental biology. In this study, we developed a computational model of the node system reported by Shinohara et al. and examined the feasibilities of the two hypotheses with a small number of cilia. With the small number of rotating cilia, flow was induced locally and global strong flow was not observed in the node. Particles were then effectively transported only when they were close to the cilia, and particle transport was strongly dependent on the ciliary positions. Although the maximum wall shear rate was also influenced by ciliary position, the mean wall shear rate at the perinodal wall increased monotonically with the number of cilia. We also investigated the membrane tension of immotile cilia, which is relevant to the regulation of mechanotransduction. The results indicated that tension of about 0.1 μN m−1 was exerted at the base even when the fluid shear rate was applied at about 0.1 s−1. The area of high tension was also localized at the upstream side, and negative tension appeared at the downstream side. Such localization may be useful to sense the flow direction at the periphery, as time-averaged anticlockwise circulation was induced in the node by rotation of a few cilia. Our numerical results support the mechanosensing hypothesis, and we expect that our study will stimulate further experimental investigations of mechanotransduction in the near future.
登录
查看更多内容
影响因子：
3.4
作者：
SKALAK, R;TOZEREN, A;CHIEN, S
通讯作者：
CHIEN, S
影响因子：
3.4
作者：
Powers, Richard J.;Roy, Sitikantha;Spector, Alexander A.
通讯作者：
Spector, Alexander A.
影响因子：
1.3
作者：
Smith, D. J.;Smith, A. A.;Blake, J. R.
通讯作者：
Blake, J. R.
DOI：
10.1002/nme.2859
发表时间：
2010-08-13
影响因子：
2.9
作者：
Walter, J.;Salsac, A. -V.;Le Tallec, P.
通讯作者：
Le Tallec, P.
影响因子：
2.2
作者：
Chen, Duanduan;Norris, Dominic;Ventikos, Yiannis
通讯作者：
Ventikos, Yiannis