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

BMC Neuroscience

Research Article

Kelly A. Glendining¹  Nuwan Dharmaratne¹  Marvin Nguyen¹  Sam C. Liu¹  Miguel A. Iglesias¹  Atomu Sawatari¹  Rajini Nagarajah¹  Catherine A. Leamey¹ 

[1] Discipline of Physiology, School of Medical Sciences and Bosch Institute, F13, University of Sydney, 2006, Sydney, NSW, Australia;

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

DOI  :  10.1186/s12868-017-0397-5

 received in 2017-03-28, accepted in 2017-11-28,  发布年份 2017

来源: Springer

【 摘 要 】

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.MethodsAnterograde 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.ResultsWe 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.ConclusionOur 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.

【 授权许可】

CC BY   
© The Author(s) 2017