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Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow.

Stevens, J; Ermakov, A; Braganca, J; Hilton, H; Underhill, P; Bhattacharya, S; Brown, NA; Norris, DP (2010) Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow. BMC DEVELOPMENTAL BIOLOGY, 10 (54). ISSN 1471-213X https://doi.org/10.1186/1471-213X-10-54
SGUL Authors: Brown, Nigel Andrew

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Abstract

BACKGROUND: Vertebrates show clear asymmetry in left-right (L-R) patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist. RESULTS: A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1), as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM). LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node. CONCLUSION: Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make Ablim1 a candidate for controlling aspects of L-R identity and patterning.

Item Type: Article
Additional Information: PubMed ID: 20487527 © 2010 Stevens et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Animals, Body Patterning, Gene Expression Regulation, Developmental, Humans, LIM Domain Proteins, Mice, Microfilament Proteins, Morphogenesis, Science & Technology, Life Sciences & Biomedicine, Developmental Biology, LEFT-RIGHT AXIS, ACTIN-BINDING, MOUSE EMBRYO, SONIC HEDGEHOG, SITUS-INVERSUS, RETINOIC ACID, EARLY STEP, C-ELEGANS, GENE, PROTEIN
Journal or Publication Title: BMC DEVELOPMENTAL BIOLOGY
ISSN: 1471-213X
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Dates:
DateEvent
20 May 2010Published
Web of Science ID: WOS:000279817000001
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URI: https://openaccess.sgul.ac.uk/id/eprint/1476
Publisher's version: https://doi.org/10.1186/1471-213X-10-54

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