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BMC Neurosci. 2017 Dec 6;18(1):78. doi: 10.1186/s12868-017-0397-5.

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

Author information

1
Discipline of Physiology, School of Medical Sciences and Bosch Institute, F13, University of Sydney, Sydney, NSW, 2006, Australia.
2
Discipline of Physiology, School of Medical Sciences and Bosch Institute, F13, University of Sydney, Sydney, NSW, 2006, Australia. cathy@physiol.usyd.edu.au.

Abstract

BACKGROUND:

The formation of visuotopically-aligned projections in the brain is required for the generation of functional binocular circuits. The mechanisms which underlie this process are unknown. Ten-m3 is expressed in a broad high-ventral to low-dorsal gradient across the retina and in topographically-corresponding gradients in primary visual centres. Deletion of Ten-m3 causes profound disruption of binocular visual alignment and function. Surprisingly, one of the most apparent neuroanatomical changes-dramatic mismapping of ipsilateral, but not contralateral, retinal axons along the representation of the nasotemporal retinal axis-does not correlate well with Ten-m3's expression pattern, raising questions regarding mechanism. The aim of this study was to further our understanding of the molecular interactions which enable the formation of functional binocular visual circuits.

METHODS:

Anterograde tracing, gene expression studies and protein pull-down experiments were performed. Statistical significance was tested using a Kolmogorov-Smirnov test, pairwise-fixed random reallocation tests and univariate ANOVAs.

RESULTS:

We show that the ipsilateral retinal axons in Ten-m3 knockout mice are mismapped as a consequence of early axonal guidance defects. The aberrant invasion of the ventral-most region of the dorsal lateral geniculate nucleus by ipsilateral retinal axons in Ten-m3 knockouts suggested changes in the expression of other axonal guidance molecules, particularly members of the EphA-ephrinA family. We identified a consistent down-regulation of EphA7, but none of the other EphA-ephrinA genes tested, as well as an up-regulation of ipsilateral-determinants Zic2 and EphB1 in visual structures. We also found that Zic2 binds specifically to the intracellular domain of Ten-m3 in vitro.

CONCLUSION:

Our findings suggest that Zic2, EphB1 and EphA7 molecules may work as effectors of Ten-m3 signalling, acting together to enable the wiring of functional binocular visual circuits.

KEYWORDS:

Binocular vision; Contralateral; EphA7; Ipsilateral; Neural development; Retina; Retinotopic mapping; Teneurin/Odz; Zic2

PMID:
29207951
PMCID:
PMC5718065
DOI:
10.1186/s12868-017-0397-5
[Indexed for MEDLINE]
Free PMC Article

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