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From zebrafish heart jogging genes to mouse and human orthologs: using Gene Ontology to investigate mammalian heart development

Khodiyar, VK; Howe, D; Talmud, PJ; Breckenridge, R; Lovering, RC; (2014) From zebrafish heart jogging genes to mouse and human orthologs: using Gene Ontology to investigate mammalian heart development. F1000Research , 2 , Article 242. 10.12688/f1000research.2-242.v2. Green open access

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Abstract

For the majority of organs in developing vertebrate embryos, left-right asymmetry is controlled by a ciliated region; the left-right organizer node in the mouse and human, and the Kuppfer's vesicle in the zebrafish. In the zebrafish, laterality cues from the Kuppfer's vesicle determine asymmetry in the developing heart, the direction of 'heart jogging' and the direction of 'heart looping'.  'Heart jogging' is the term given to the process by which the symmetrical zebrafish heart tube is displaced relative to the dorsal midline, with a leftward 'jog'. Heart jogging is not considered to occur in mammals, although a leftward shift of the developing mouse caudal heart does occur prior to looping, which may be analogous to zebrafish heart jogging. Previous studies have characterized 30 genes involved in zebrafish heart jogging, the majority of which have well defined orthologs in mouse and human and many of these orthologs have been associated with early mammalian heart development.    We undertook manual curation of a specific set of genes associated with heart development and we describe the use of Gene Ontology term enrichment analyses to examine the cellular processes associated with heart jogging.  We found that the human, mouse and zebrafish 'heart jogging orthologs' are involved in similar organ developmental processes across the three species, such as heart, kidney and nervous system development, as well as more specific cellular processes such as cilium development and function. The results of these analyses are consistent with a role for cilia in the determination of left-right asymmetry of many internal organs, in addition to their known role in zebrafish heart jogging.    This study highlights the importance of model organisms in the study of human heart development, and emphasises both the conservation and divergence of developmental processes across vertebrates, as well as the limitations of this approach.

Type: Article
Title: From zebrafish heart jogging genes to mouse and human orthologs: using Gene Ontology to investigate mammalian heart development
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.12688/f1000research.2-242.v2
Publisher version: http://dx.doi.org/10.12688/f1000research.2-242.v2
Language: English
Additional information: © 2014 Khodiyar VK et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). - See more at: http://f1000research.com/articles/2-242/v2#sthash.rHpw4vcC.dpuf
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/1423861
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