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Ethanol alters gene expression and cell organisation during optic vesicle evagination.

Santos-Ledo, A; Cavodeassi, F; Carreño, H; Aijón, J; Arévalo, R; (2013) Ethanol alters gene expression and cell organisation during optic vesicle evagination. Neuroscience , 250 pp. 493-506. 10.1016/j.neuroscience.2013.07.036. Green open access

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Abstract

Ethanol has been described as a teratogen in vertebrate development. During early stages of brain formation, ethanol affects the evagination of the optic vesicles, resulting in synophthalmia or cyclopia, phenotypes where the optic vesicles partially or totally fuse. The mechanisms by which ethanol affects the morphogenesis of the optic vesicles are however largely unknown. In this study we make use of in situ hybridization, electron microscopy and immunohistochemistry to show that ethanol has profound effects on cell organisation and gene expression during the evagination of the optic vesicles. Exposure to ethanol during early eye development alters the expression patterns of some genes known to be important for eye morphogenesis, such as rx3/1 and six3a. Furthermore, exposure to ethanol interferes with the acquisition of neuroepitelial features by the eye field cells, which is clear at ultrastructual level. Indeed, ethanol disrupts the acquisition of fusiform cellular shapes within the eye field. In addition, tight junctions do not form and retinal progenitors do not properly polarize, as suggested by the mis-localization and down-regulation of zo1. We also show that the ethanol-induced cyclopic phenotype is significantly different to that observed in cyclopic mutants, suggesting a complex effect of ethanol on a variety of targets. Our results show that ethanol not only disrupts the expression pattern of genes involved in retinal morphogenesis, such as rx3 and rx1, but also disrupts the changes in cell polarity that normally occur during eye field splitting. Thus, ethylic teratology seems to be related not only to modifications in gene expression and cell death but also to alterations in cell morphology.

Type: Article
Title: Ethanol alters gene expression and cell organisation during optic vesicle evagination.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuroscience.2013.07.036
Publisher version: http://dx.doi.org/10.1016/j.neuroscience.2013.07.0...
Additional information: �© 2013 IBRO. Published by Elsevier Ltd. All rights reserved. This work is licensed under a Creative Commons Attribution 3.0 Unported License.
Keywords: Cell polarity, Cyclopic mutants, Eye specification, Morphogenesis
UCL classification: UCL > Provost and Vice Provost Offices
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1406063
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