| Laterality defects are influenced by timing of treatments and animal model. | |
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MedLine Citation:
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PMID: 22099174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The timing of when the embryonic left-right (LR) axis is first established and the mechanisms driving this process are subjects of strong debate. While groups have focused on the role of cilia in establishing the LR axis during gastrula and neurula stages, many animals appear to orient the LR axis prior to the appearance of, or without the benefit of, motile cilia. Because of the large amount of data available in the published literature and the similarities in the type of data collected across laboratories, I have examined relationships between the studies that do and do not implicate cilia, the choice of animal model, the kinds of LR patterning defects observed, and the penetrance of LR phenotypes. I found that treatments affecting cilia structure and motility had a higher penetrance for both altered gene expression and improper organ placement compared to treatments that affect processes in early cleavage stage embryos. I also found differences in penetrance that could be attributed to the animal models used; the mouse is highly prone to LR randomization. Additionally, the data were examined to address whether gene expression can be used to predict randomized organ placement. Using regression analysis, gene expression was found to be predictive of organ placement in frogs, but much less so in the other animals examined. Together, these results challenge previous ideas about the conservation of LR mechanisms, with the mouse model being significantly different from fish, frogs, and chick in almost every aspect examined. Additionally, this analysis indicates that there may be missing pieces in the molecular pathways that dictate how genetic information becomes organ positional information in vertebrates; these gaps will be important for future studies to identify, as LR asymmetry is not only a fundamentally fascinating aspect of development but also of considerable biomedical importance. |
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Authors:
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Laura N Vandenberg |
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Publication Detail:
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Type: Journal Article; Meta-Analysis; Research Support, U.S. Gov't, P.H.S. Date: 2011-10-04 |
Journal Detail:
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Title: Differentiation; research in biological diversity Volume: 83 ISSN: 1432-0436 ISO Abbreviation: Differentiation Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-11-21 Completed Date: 2012-03-20 Revised Date: 2013-02-20 |
Medline Journal Info:
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Nlm Unique ID: 0401650 Medline TA: Differentiation Country: England |
Other Details:
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Languages: eng Pagination: 26-37 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 International Society of Differentiation. Published by Elsevier B.V. All rights reserved. |
Affiliation:
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Tufts University, Center for Regenerative & Developmental Biology and Department of Biology, Medford, MA 02155, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Patterning* Cilia / genetics*, physiology* Embryonic Development / genetics* Gastrula / growth & development* Gene Expression Regulation, Developmental Ions / metabolism Mice Models, Animal Mutation Phenotype Signal Transduction / genetics Xenopus / embryology, genetics |
| Grant Support | |
ID/Acronym/Agency:
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1F32GM087107/GM/NIGMS NIH HHS; F32 GM087107-02/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ions |
| Comments/Corrections | |
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