Loss of zebrafish dzip1 results in inappropriate recruitment of periocular mesenchyme to the optic fissure and ocular coloboma.

Sri Pratima Nandamuri,Kristen M Kwan,Sarah Lusk

doi:10.1371/journal.pone.0265327

Abstract

Cilia are essential for the development and function of many different tissues. Although cilia machinery is crucial in the eye for photoreceptor development and function, a role for cilia in early eye development and morphogenesis is still somewhat unclear: many zebrafish cilia mutants retain cilia at early stages due to maternal deposition of cilia components. An eye phenotype has been described in the mouse Arl13 mutant, however, zebrafish arl13b is maternally deposited, and an early role for cilia proteins has not been tested in zebrafish eye development. Here we use the zebrafish dzip1 mutant, which exhibits a loss of cilia throughout stages of early eye development, to examine eye development and morphogenesis. We find that in dzip1 mutants, initial formation of the optic cup proceeds normally, however, the optic fissure subsequently fails to close and embryos develop the structural eye malformation ocular coloboma. Further, neural crest cells, which are implicated in optic fissure closure, do not populate the optic fissure correctly, suggesting that their inappropriate localization may be the underlying cause of coloboma. Overall, our results indicate a role for dzip1 in proper neural crest localization in the optic fissure and optic fissure closure.

Highlights

Vertebrate eye development, comprising numerous conserved gene regulatory networks and morphogenetic processes, begins with the emergence, or evagination, of optic vesicles from the ventral forebrain
The cilia machinery is required for vision, in the context of photoreceptor development and function: conserved components are an integral part of the connecting cilium, dzip1 mutant causes ocular coloboma in zebrafish which links the inner and outer segments [26–28]
The zebrafish dzip1 mutant exhibits a loss of cilia by 10 hpf [49], a time when the zebrafish eye just commences evagination, making this a useful system to ask questions regarding cilia and Hh signaling in optic cup morphogenesis, to understand how coloboma might arise in ciliopathy conditions, and how Hh signaling is affected in the zebrafish eye in the absence of cilia

Summary

Introduction

Vertebrate eye development, comprising numerous conserved gene regulatory networks and morphogenetic processes, begins with the emergence, or evagination, of optic vesicles from the ventral forebrain. Formation of a precise and stereotyped eye structure is crucial for visual function, and morphological aberrations of the eye are a common cause of human visual impairments. One such visual impairment condition is ocular coloboma, which accounts for ~10% of pediatric blindness worldwide. Coloboma is caused by defective development and morphogenesis of a specific structure in the eye, the optic fissure.

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