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脊椎动物左右对称破缺过程中的节点不对称与刺猬信号通路

Nodal asymmetry and hedgehog signaling during vertebrate left-right symmetry breaking.

作者信息

Negretti Maria Isabella, Böse Nina, Petri Natalia, Kremnyov Stanislav, Tsikolia Nikoloz

机构信息

Anatomy and Embryology, University Medical Center Göttingen, Göttingen, Germany.

Department of Embryology, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.

出版信息

Front Cell Dev Biol. 2022 Sep 12;10:957211. doi: 10.3389/fcell.2022.957211. eCollection 2022.

DOI:10.3389/fcell.2022.957211
PMID:36172285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9511907/
Abstract

Development of visceral left-right asymmetry in bilateria is based on initial symmetry breaking followed by subsequent asymmetric molecular patterning. An important step is the left-sided expression of transcription factor which is mediated by asymmetric expression of the morphogen in the left lateral plate mesoderm of vertebrates. Processes leading to emergence of the asymmetric domain differ depending on the mode of symmetry breaking. In and mouse embryos, the leftward fluid flow on the ventral surface of the left-right organizer leads through intermediate steps to enhanced activity of the nodal protein on the left side of the organizer and subsequent asymmetric induction in the lateral plate mesoderm. In the chick embryo, asymmetric morphogenesis of axial organs leads to paraxial asymmetry during the late gastrulation stage. Although it was shown that hedgehog signaling is required for initiation of the expression, the mechanism of its asymmetry remains to be clarified. In this study, we established the activation of hedgehog signaling in early chick embryos to further study its role in the initiation of asymmetric expression. Our data reveal that hedgehog signaling is sufficient to induce the expression in competent domains of the chick embryo, while treatment of embryos led to moderate inhibition. We discuss the role of symmetry breaking and competence in the initiation of asymmetric gene expression.

摘要

两侧对称动物内脏左右不对称的发育基于最初的对称性打破,随后是不对称的分子模式形成。一个重要步骤是转录因子在左侧的表达,这是由脊椎动物左侧侧板中胚层中形态发生素的不对称表达介导的。导致不对称结构域出现的过程因对称性打破的方式而异。在斑马鱼和小鼠胚胎中,左右组织者腹侧表面的向左流体流动通过中间步骤导致组织者左侧结节蛋白的活性增强,随后在侧板中胚层诱导不对称。在鸡胚胎中,轴向器官的不对称形态发生在原肠胚形成后期导致近轴的不对称。尽管已表明刺猬信号通路是启动表达所必需的,但其不对称机制仍有待阐明。在本研究中,我们在早期鸡胚胎中建立了刺猬信号通路的激活,以进一步研究其在不对称表达启动中的作用。我们的数据表明,刺猬信号通路足以在鸡胚胎的感受态结构域中诱导表达,而对胚胎的处理导致适度的抑制。我们讨论了对称性打破和感受态在不对称基因表达启动中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/c6529af90cb3/fcell-10-957211-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/07ac3e090332/fcell-10-957211-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/fdfb75f8bbe4/fcell-10-957211-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/131cca804023/fcell-10-957211-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/c6529af90cb3/fcell-10-957211-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/07ac3e090332/fcell-10-957211-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/fdfb75f8bbe4/fcell-10-957211-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/131cca804023/fcell-10-957211-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fe5/9511907/c6529af90cb3/fcell-10-957211-g004.jpg

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Nat Genet. 2022 Jan;54(1):62-72. doi: 10.1038/s41588-021-00970-4. Epub 2021 Dec 13.
2
Bicc1 and Dicer regulate left-right patterning through post-transcriptional control of the Nodal inhibitor Dand5.Bicc1 和 Dicer 通过对 Nodal 抑制剂 Dand5 的转录后控制调节左右模式形成。
Nat Commun. 2021 Sep 16;12(1):5482. doi: 10.1038/s41467-021-25464-z.
3
Diversity of left-right symmetry breaking strategy in animals.
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Dev Dyn. 2025 Aug;254(8):950-964. doi: 10.1002/dvdy.722. Epub 2024 Jun 27.
动物左右对称打破策略的多样性。
F1000Res. 2020 Feb 19;9. doi: 10.12688/f1000research.21670.1. eCollection 2020.
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Nodal paralogues underlie distinct mechanisms for visceral left-right asymmetry in reptiles and mammals.节段同源物为爬行动物和哺乳动物内脏左右不对称提供了不同的机制。
Nat Ecol Evol. 2020 Feb;4(2):261-269. doi: 10.1038/s41559-019-1072-2. Epub 2020 Jan 6.
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Cilia-driven asymmetric Hedgehog signalling determines the amphioxus left-right axis by controlling expression.纤毛驱动的非对称 Hedgehog 信号通过控制 表达来决定文昌鱼的左右轴。
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