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Downstream mediators of Ten-m3 signalling in the developing visual pathway

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Glendining, KA, Liu, SC, Nguyen, M, Dharmaratne, N, Nagarajah, R, Iglesias, MA ORCID: 0000-0001-5781-2091, Sawatari, A and Leamey, CA 2017 , 'Downstream mediators of Ten-m3 signalling in the developing visual pathway' , BMC neuroscience, vol. 18, no. 1 , pp. 1-17 , doi: 10.1186/s12868-017-0397-5.

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Abstract

Background: The formation of visuotopically-aligned projections in the brain is required for the generation of functionalbinocular circuits. The mechanisms which underlie this process are unknown. Ten-m3 is expressed in a broadhigh-ventral to low-dorsal gradient across the retina and in topographically-corresponding gradients in primary visualcentres. Deletion of Ten-m3 causes profound disruption of binocular visual alignment and function. Surprisingly, oneof the most apparent neuroanatomical changes—dramatic mismapping of ipsilateral, but not contralateral, retinalaxons along the representation of the nasotemporal retinal axis—does not correlate well with Ten-m3’s expressionpattern, raising questions regarding mechanism. The aim of this study was to further our understanding of themolecular interactions which enable the formation of functional binocular visual circuits.Methods: Anterograde tracing, gene expression studies and protein pull-down experiments were performed. Statisticalsignifcance was tested using a Kolmogorov–Smirnov test, pairwise-fxed random reallocation tests and univariateANOVAs.Results: We show that the ipsilateral retinal axons in Ten-m3 knockout mice are mismapped as a consequenceof early axonal guidance defects. The aberrant invasion of the ventral-most region of the dorsal lateral geniculatenucleus by ipsilateral retinal axons in Ten-m3 knockouts suggested changes in the expression of other axonal guidancemolecules, particularly members of the EphA–ephrinA family. We identifed a consistent down-regulation ofEphA7, but none of the other EphA–ephrinA genes tested, as well as an up-regulation of ipsilateral-determinants Zic2and EphB1 in visual structures. We also found that Zic2 binds specifcally to the intracellular domain of Ten-m3 in vitro.Conclusion: Our fndings suggest that Zic2, EphB1 and EphA7 molecules may work as efectors of Ten-m3 signalling,acting together to enable the wiring of functional binocular visual circuits.

Item Type: Article
Authors/Creators:Glendining, KA and Liu, SC and Nguyen, M and Dharmaratne, N and Nagarajah, R and Iglesias, MA and Sawatari, A and Leamey, CA
Keywords: visual development, visual system, embriology
Journal or Publication Title: BMC neuroscience
Publisher: Biomed Central Ltd
ISSN: 1471-2202
DOI / ID Number: 10.1186/s12868-017-0397-5
Copyright Information:

Copyright 2017 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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