Molecular regulation of visual system development: more than meets the eye

Abstract

Vertebrate eye development has been an excellent model system to investigate basic concepts of developmental biology ranging from mechanisms of tissue induction to the complex patterning and bidimensional orientation of the highly specialized retina. Recent advances have shed light on the interplay between numerous transcriptional networks and growth factors that are involved in the specific stages of retinogenesis, optic nerve formation, and topographic mapping. In this review, we summarize this recent progress on the molecular mechanisms underlying the development of the eye, visual system, and embryonic tumors that arise in the optic system.For humans, the visual system is a principal conduit for acquiring external sensory information. Thus, "quality of vision" is intimately tied with "quality of life." Despite extensive clinical and laboratory investigation, many diseases that impair vision, ranging from congenital abnormalities to sporadic forms of retinal degeneration, lack effective treatments. One hope is that improved understanding of development of the visual system, from the eye to the visual cortex, will provide insight into methods for attenuating or reversing these disorders. Development of the neural retina and visual system, especially the mechanism of axon remodeling during synaptogenesis, is complex. Studies have shown that numerous genes are involved in the differentiation and formation of the retina acting at specific stages of the development of visual system. In this review, we will summarize recent progress on the molecular mechanisms underlying the development of the eye and visual system. Anatomy of eye developmentThe basic components of the complex optic system are derived from four embryonic sources: forebrain neuroectoderm, intercalating mesoderm, surface ectoderm, and neural crest (Fig. 1). The neuroectoderm differentiates into the retina, iris, and optic nerve; the surface ectoderm gives rise to lens and corneal epithelium; the mesoderm differentiates into the extraocular muscles and the fibrous and vascular coats of the eye; and neural crest cells become the corneal stroma sclera and corneal endothelium. The vertebrate eye originates from bilateral telencephalic optic grooves. In humans, optic vesicles emerge at the end of the fourth week of development and soon thereafter contact the surface ectoderm to induce lens formation. When the lens placode invaginates to form the lens vesicle, the distal part of optic vesicle begins to invaginate to form the optic cup. As the optic vesicles grow, the proximal ends expand and their connections with the forebrain constrict to form optic stalks. Through the retinal fissure, a groove at the inferior aspect of the optic vesicle, the hyaloid artery, enters the eye and nourishes the optic cup and lens vesicle. The retinal fissure normally closes at ∼7 wk of development, and proximal parts of the hyaloid vessels persist to form the central artery and vein of the retina, a branch of the ophthalmic artery. Defects in closure of the fissure result in...

Endogenous Gradients of Resting Potential Instructively Pattern Embryonic Neural Tissue via Notch Signaling and Regulation of Proliferation

“…defects were also seen, but these embryos usually did not survive to stage 45. Eye development (which is dependent on proper neural development; Harada et al, 2007;Fuhrmann, 2010;Zuber, 2010) was also affected, resulting in incompletely formed eyes, eyes fused to the brain, and pigmented optic nerves (data not shown) as previously documented (Pai et al, 2012b).…”

Acheate‐scute like 1 (Ascl1) is required for normal delta‐like (Dll) gene expression and notch signaling during retinal development

“…Many bHLH homologs are expressed in the vertebrate retina, but only Ascl1 and Neurog2 are expressed in mitotically active progenitors (Jasoni et al, 1994;Jasoni and Reh, 1996;Perron et al, 1998;Yan et al, 2001;Marquardt, et al, 2001;Ma and Wang, 2006;Le et al, 2006;Nelson and Reh, 2008). While the functions of proneural bHLH genes have been extensively investigated with respect to their role in retinal cell fate specification (reviewed by Cepko, 1999;Vetter and Brown, 2001;Yan et al, 2005;Ohsawa and Kageyama, 2007;Harada et al, 2007), their function in the regulation Notch ligands have not been described in the developing retina. Recently, we found in the developing chick retina that the expression pattern and expression kinetics of Dll1 during synchronized progenitor differentiation most closely matched that of Ascl1, similar to observations in the frog retina (Perron et al, 1998).…”

Strategies for retinal cell generation from human pluripotent stem cells

“…This process is coordinated in time and space by both intrinsic and extrinsic factors (53). Eventually the progenitor pool begins to divide asymmetrically to generate daughter cells that can adopt differing fates during development (54).…”