The potential role of Arhgef33 RhoGEF in foveal development in the zebra finch retina

Takefumi Sugiyama,Tetsuo Kon,Taro Chaya,Yoshihiro Omori,Takahisa Furukawa,Dai Watanabe,Kentaro Abe,Yutaka Suzuki,Haruka Yamamoto

doi:10.1038/s41598-020-78452-6

Abstract

The fovea is a pit formed in the center of the retina that enables high-acuity vision in certain vertebrate species. While formation of the fovea fascinates many researchers, the molecular mechanisms underlying foveal development are poorly understood. In the current study, we histologically investigated foveal development in zebra finch (Taeniopygia guttata) and found that foveal pit formation begins just before post-hatch day 14 (P14). We next performed RNA-seq analysis to compare gene expression profiles between the central (foveal and parafoveal) and peripheral retina in zebra finch at P14. We found that the Arhgef33 expression is enriched in the middle layer of the inner nuclear layer at the parafovea, suggesting that Arhgef33 is dominantly expressed in Müller glial cells in the developing parafovea. We then performed a pull-down assay using Rhotekin-RBD and observed GEF activity of Arhgef33 against RhoA. We found that overexpression of Arhgef33 in HEK293 cells induces cell contraction and that Arhgef33 expression inhibits neurite extension in Neuro 2A cells, which is partially recovered by a Rho-kinase (ROCK) inhibitor. Taken together, we used zebra finch as a model animal to investigate foveal development and identified Arhgef33 as a candidate protein possibly involved in foveal development through modulating RhoA activity.

Highlights

High acuity of human vision largely depends on the fovea, which is a ‘pit’ structure formed at the center of the macula in the retina
It is likely that the basic molecular mechanisms underlying foveal development are conserved among species, because basic retinal structures and the foveal pit formation timing which begins after the completion of retinal layer differentiation are conserved[1, 3]
We observed that the foveal pit in zebra finch retina begins formation between P10 and post-hatch day 14 (P14)

Summary

Introduction

High acuity of human vision largely depends on the fovea, which is a ‘pit’ structure formed at the center of the macula in the retina. We examined foveal development using the zebra finch retina at several developmental stages.

Results

Conclusion