Coordinated morphogenetic mechanisms shape the vertebrate eye

Abstract

The molecular bases of vertebrate eye formation have been extensively investigated during the past 20 years. This has resulted in the definition of the backbone of the gene regulatory networks controlling the different steps of eye development and has further highlighted a substantial conservation of these networks among vertebrates. Yet, the precise morphogenetic events allowing the formation of the optic cup from a small group of cells within the anterior neural plate are still poorly understood. It is also unclear if the morphogenetic events leading to eyes of very similar shape are indeed comparable among all vertebrates or if there are any species-specific peculiarities. Improved imaging techniques have enabled to follow how the eye forms in living embryos of a few vertebrate models, whereas the development of organoid cultures has provided fascinating tools to recapitulate tissue morphogenesis of other less accessible species. Here, we will discuss what these advances have taught us about eye morphogenesis, underscoring possible similarities and differences among vertebrates. We will also discuss the contribution of cell shape changes to this process and how morphogenetic and patterning mechanisms integrate to assemble the final architecture of the eye. The development of the vertebrate eye has attracted the interest of classical embryologists for more than a century and that of modern developmental geneticists for the past two decades (Spemann, 1901; Chow and Lang, 2001). This continuous interest is possibly linked to several of it characteristics. For example, the eye is much more accessible to experimental manipulations than the rest of the Central Nervous System (CNS); it is also an ideal model to study signaling and inductive events, as its formation involves the interaction among different tissues including the neural and non-neural ectoderm, the axial meso-endoderm, and the periocular mesenchyme (Fuhrmann, 2010; Sinn and Wittbrodt, 2013; Bazin-Lopez et al., 2015). The multi-branched evolutionary history behind the emergence of visual organs from an ancestral prototypic eye has also attracted the attention of researchers in the evo-devo field, converting the eye to an excellent tool for morphological and molecular evolutionary studies (Arendt, 2003; Letelier et al., 2017). The latter have helped to understand the logic of their gene regulatory networks and have established that vertebrate eye formation depends on the reiterative use of a core set of regulatory molecules highly conserved among invertebrates and vertebrates (Fuhrmann, 2010; Beccari et al., 2013). These gene regulatory networks are described in several comprehensive reviews to which the readers are referred to (Chow and Lang, 2001; Martinez-Morales et al., 2004; Adler and Canto-Soler, 2007; Fuhrmann, 2010; Cavodeassi and Houart, 2012; Beccari et al., 2013; Amram et al., 2017). Old morphological studies based on static images together with more recent molecular studies have also established that eye formation starts with the specification of eye field within the anterior neural plate (ANP), followed by their lateral protrusion to form the optic vesicles, and the infolding of the vesicles into bi-layered optic cups (Hilfer, 1983; Schmitt and Dowling, 1994; Li et al., 2000; Kwan et al., 2012).