Morphogenesis and axis specification occur in parallel during optic cup and optic fissure formation, differentially modulated by BMP and Wnt.

Priska Eckert,Joachim Wittbrodt,Lucas Schütz,Max D Knickmeyer,Stephan Heermann

doi:10.1098/rsob.180179

Abstract

Optic cup morphogenesis is an intricate process. Especially, the formation of the optic fissure is not well understood. Persisting optic fissures, termed coloboma, are frequent causes for congenital blindness. Even though the defective fusion of the fissure margins is the most acknowledged reason for coloboma, highly variable morphologies of coloboma phenotypes argue for a diverse set of underlying pathomechanisms. Here, we investigate optic fissure morphogenesis in zebrafish to identify potential morphogenetic defects resulting in coloboma. We show that the formation of the optic fissure depends on tissue flow movements, integrated into the bilateral distal epithelial flow forming the optic cup. On the temporal side, the distal flow translates into a ventral perpendicular flow, shaping the temporal fissure margin. On the nasal side, however, the distal flow is complemented by tissue derived from the optic stalk, shaping the nasal fissure margin. Notably, a distinct population of TGFβ-signalling positive cells is translocated from the optic stalk into both fissure margins. Furthermore, we show that induced BMP signalling as well as Wnt-signalling inhibition result in morphogenetic defects of the optic fissure. Our data also indicate that morphogenesis is crucial for a proper positioning of pre-specified dorsal–ventral optic cup domains.

Highlights

Eye morphogenesis in vertebrates is a complex process during which initially optic vesicles evaginate from the eye field, located within the late prosencephalon [1,2,3]
We provide evidence that tissue dynamics are essential for optic fissure morphogenesis and that these are largely affected by BMP and Wnt-signalling
Even though the role of tissue dynamics is more and more appreciated for optic cup formation [18,22 –25], only very little was so far known about optic fissure morphogenesis and whether or not this is affected by tissue dynamics

Summary

Introduction

Eye morphogenesis in vertebrates is a complex process during which initially optic vesicles evaginate from the eye field, located within the late prosencephalon [1,2,3]. These optic vesicles are transformed into bi-layered optic cups [4,5]. A plethora of genes have been linked to coloboma formation [7], resulting in a coloboma gene network [8,9] This network is growing and consists among others of components of various signalling pathways, such as Wnt [10,11], FGF [12,13], RA [14,15], Hippo [16], Shh [17] BMP [18] and TGFb [19]. Alterations in some result in a subtle coloboma phenotype [12,13,19],

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Results

Conclusion