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左右发育过程中纤毛长度的动态变化

Dynamics of cilia length in left-right development.

作者信息

Pintado P, Sampaio P, Tavares B, Montenegro-Johnson T D, Smith D J, Lopes S S

机构信息

NOVA Medical School Faculdade de Ciências Médicas, Chronic Diseases Research Centre, CEDOC , Universidade Nova de Lisboa , Campo Mártires da Pátria, 130, 1169-056 Lisboa , Portugal.

School of Mathematics , University of Birmingham , Birmingham , UK.

出版信息

R Soc Open Sci. 2017 Mar 8;4(3):161102. doi: 10.1098/rsos.161102. eCollection 2017 Mar.

DOI:10.1098/rsos.161102
PMID:28405397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5383854/
Abstract

Reduction in the length of motile cilia in the zebrafish left-right organizer (LRO), also known as Kupffer's vesicle, has a large impact on left-right development. Here we demonstrate through genetic overexpression in zebrafish embryos and mathematical modelling that the impact of increased motile cilia length in embryonic LRO fluid flow is milder than that of short cilia. Through Arl13b overexpression, which increases cilia length without impacting cilia beat frequency, we show that the increase in cilium length is associated with a decrease in beat amplitude, resulting in similar flow strengths for Arl13b overexpression and wild-type (WT) embryos, which were not predicted by current theory. Longer cilia exhibit pronounced helical beat patterns and, consequently, lower beat amplitudes relative to WT, a result of an elastohydrodynamic shape transition. For long helical cilia, fluid dynamics modelling predicts a mild (approx. 12%) reduction in the torque exerted on the fluid relative to the WT, resulting in a proportional reduction in flow generation. This mild reduction is corroborated by experiments, providing a mechanism for the mild impact on organ .

摘要

斑马鱼左右组织者(LRO),即库普弗囊泡中活动纤毛长度的缩短,对左右发育有很大影响。在这里,我们通过在斑马鱼胚胎中的基因过表达和数学建模证明,胚胎LRO中活动纤毛长度增加对流体流动的影响比短纤毛的影响要小。通过过表达Arl13b来增加纤毛长度而不影响纤毛摆动频率,我们发现纤毛长度的增加与摆动幅度的减小有关,这导致Arl13b过表达胚胎和野生型(WT)胚胎的流动强度相似,而这是当前理论所无法预测的。更长的纤毛表现出明显的螺旋摆动模式,因此相对于WT摆动幅度更低,这是弹性流体动力学形状转变的结果。对于长螺旋纤毛,流体动力学建模预测相对于WT,施加在流体上的扭矩会轻微降低(约12%),从而导致流动产生成比例降低。实验证实了这种轻微降低,为对器官的轻微影响提供了一种机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c917/5383854/daf8718df6bb/rsos161102-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c917/5383854/5c6bac8614b9/rsos161102-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c917/5383854/88af0664b509/rsos161102-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c917/5383854/daf8718df6bb/rsos161102-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c917/5383854/5c6bac8614b9/rsos161102-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c917/5383854/88af0664b509/rsos161102-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c917/5383854/daf8718df6bb/rsos161102-g3.jpg

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The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR.斑马鱼的库普弗囊泡作为一种模型系统,用于研究多囊蛋白-2缺乏导致囊性纤维化跨膜传导调节因子(CFTR)激活的分子机制。
Biol Open. 2015 Oct 2;4(11):1356-66. doi: 10.1242/bio.014076.
3
Organized chaos in Kupffer's vesicle: how a heterogeneous structure achieves consistent left-right patterning.
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Front Cell Dev Biol. 2022 Dec 23;10:1035513. doi: 10.3389/fcell.2022.1035513. eCollection 2022.
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Crosstalk between cilia and autophagy: implication for human diseases.纤毛与自噬的相互作用:与人类疾病的关联。
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