Molecular mechanisms of optic vesicle development: complexities, ambiguities and controversies

Abstract

Optic vesicle formation, transformation into an optic cup and integration with neighboring tissues are essential for normal eye formation, and involve the coordinated occurrence of complex cellular and molecular events. Perhaps not surprisingly, these complex phenomena have provided fertile ground for controversial and even contradictory results and conclusions. After presenting an overview of current knowledge of optic vesicle development, we will address conceptual and methodological issues that complicate research in this field. This will be done through a review of the pertinent literature, as well as by drawing on our own experience, gathered through recent studies of both intra- and extra-cellular regulation of optic vesicle development and patterning. Finally, and without attempting to be exhaustive, we will point out some important aspects of optic vesicle development that have not yet received enough attention.

Figure 1

Schematic representation of vertebrate eye development. A. The optic vesicle forms as an evagination from the diencephalon. B. Upon contact with the surface ectoderm, the optic vesicle becomes patterned into presumptive RPE, neural retina and optic stalk; the surface ectoderm in turn forms the lens placode. C. The optic vesicle and lens placode invaginate, giving rise to the optic cup and the lens vesicle, respectively. C′. The ventral region of the invaginating optic vesicle forms the choroid fissure. D-E. Transition from early to mature optic cup. The lens vesicle loses its cavity and becomes a solid structure; the neural retina and the pigment epithelium become apposed, reducing ependymal cavity to a virtual space; the optic stalk gives rise to the optic nerve, and the surface ectoderm adjacent to the lens gives rise to the corneal epithelium. Abbreviations: C: Cornea; L: lens; LP: lens placode; LV: lens vesicle; MS: mesenchyme; NR: neural retina; ON: optic nerve; OS: optic stalk; OV: optic vesicle; RPE: retinal pigment epithelium; S: sclera; SE: surface ectoderm.

Figure 2

Schematic representation of the distribution of members of several families of extracellular signaling systems in the developing optic cup. The data shown corresponds predominantly to in situ hybridization results. Gradients of color represent the superposition of expression domains of different molecules, rather than gradients of expression of individual molecules (for the sake of clarity, only the region corresponding to the highest level of expression has been represented for those molecules whose pattern of expression follows high-to-low gradients). A. BMPs, its receptors, antagonists and inhibitors (modified and up-dated from Belecky-Adams, unpublished). B. Wnts, its receptors and antagonists (modified and up-dated from Van Raay and Vetter, 2004). C. FGFs, its receptors and antagonists. Abbreviations: BMP: bone morphogenetic proteins; CRF: cysteine-rich FGF receptors; Dan: members of the Dan protein family; FGF: fibroblast growth factors; Fz: frizzled receptors; Sfrp: secreted frizzled related proteins; Spry: sprouty protein; Wnt: members of the Wnt family.