Light-induced asymmetries in embryonic retinal gene expression are mediated by the vascular system and extracellular matrix

Abstract

Left–right asymmetries in the nervous system (lateralisation) influence a broad range of behaviours, from social responses to navigation and language. The role and pathways of endogenous and environmental mechanisms in the ontogeny of lateralisation remains to be established. The domestic chick is a model of both endogenous and experience-induced lateralisation driven by light exposure. Following the endogenous rightward rotation of the embryo, the asymmetrical position in the egg results in a greater exposure of the right eye to environmental light. To identify the genetic pathways activated by asymmetric light stimulation, and their time course, we exposed embryos to different light regimes: darkness, 6 h of light and 24 h of light. We used RNA-seq to compare gene expression in the right and left retinas and telencephalon. We detected differential gene expression in right vs left retina after 6 h of light exposure. This difference was absent in the darkness condition and had already disappeared by 24 h of light exposure, suggesting that light-induced activation is a self-terminating phenomenon. This transient effect of light exposure was associated with a downregulation of the sensitive-period mediator gene DIO2 (iodothyronine deiodinase 2) in the right retina. No differences between genes expressed in the right vs. left telencephalon were detected. Gene networks associated with lateralisation were connected to vascularisation, cell motility, and the extracellular matrix. Interestingly, we know that the extracellular matrix—including the differentially expressed PDGFRB gene—is involved in morphogenesis, sensitive periods, and in the endogenous chiral mechanism of primary cilia, that drives lateralisation. Our data show a similarity between endogenous and experience-driven lateralisation, identifying functional gene networks that affect lateralisation in a specific time window.

Brain asymmetry as minimization of free energy: a theoretical model

“…Examples are apparent in various consistent biases favouring one or the other side for either motoric or sensory activities. For instance, animals with laterally placed eyes (and sometimes also those with large binocular overlaps) systematically use their left or right eye in selecting prey, emitting agonistic responses, responding to predators, sleeping, or responding to social signals (for general reviews including also different sensory modalities see [6][7][8][9][10] and for recent results involving causal mechanisms see [11][12][13][14]). Evidence for behavioural and brain asymmetries is widespread and not limited at all to only vertebrates, ranging from the nematodes Caenorhabditis elegans [15] to human beings [16].…”

Cytoscape stringApp 2.0: Analysis and Visualization of Heterogeneous Biological Networks

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