ArticleNature2017
A right-handed signalling pathway drives heart looping in vertebrates.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
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- Imaging Approaches and the Quantitative Analysis of Heart Development.Journal of cardiovascular development and disease · 2023Review
- Left-Sided Heart Defects and Laterality Disturbance in Hypoplastic Left Heart Syndrome.Journal of cardiovascular development and disease · 2023Review
- LOF variants identifying candidate genes of laterality defects patients with congenital heart disease.PLoS genetics · 2022Article
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- Epithelial-mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities.MedComm · 2022Review
- Pseudodynamic analysis of heart tube formation in the mouse reveals strong regional variability and early left-right asymmetry.Nature cardiovascular research · 2022Article
- Sequential action of JNK genes establishes the embryonic left-right axis.Development (Cambridge, England) · 2022Article
- Post-Transcriptional Regulation of Molecular Determinants during Cardiogenesis.International journal of molecular sciences · 2022Review
- Modeling Human Cardiac Arrhythmias: Insights from Zebrafish.Journal of cardiovascular development and disease · 2022Review
- Understanding laterality disorders and the left-right organizer: Insights from zebrafish.Frontiers in cell and developmental biology · 2022Review
- Tbx5a and Tbx5b paralogues act in combination to control separate vectors of migration in the fin field of zebrafish.Developmental biology · 2022Article
- Left-handed cardiac looping by cell chirality is mediated by position-specific convergent extensions.Biophysical journal · 2021Article
- Prrx1b restricts fibrosis and promotes Nrg1-dependent cardiomyocyte proliferation during zebrafish heart regeneration.Development (Cambridge, England) · 2021Article
- Pitx controls amphioxus asymmetric morphogenesis by promoting left-side development and repressing right-side formation.BMC biology · 2021Article
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8 authors at 4 institutions in 2 countries.
Funding
Abstract
Most animals show external bilateral symmetry, which hinders the observation of multiple internal left-right (L/R) asymmetries that are fundamental to organ packaging and function. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail1 (refs 3, 4). Despite some existing evidence, it remains unclear whether an equivalent instructive pathway provides right-hand-specific information to the embryo. Here we show that, in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline, leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right lateral plate mesoderm, converge on the asymmetric activation of the transcription factors Pitx2 and Prrx1, which integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo, and in the mouse SNAIL1 acts in a similar manner to Prrx1a in zebrafish and PRRX1 in the chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.