Chapter Ten - Lens Development and Crystallin Gene Expression
Introduction
Embryonic lens development is a critical step during eye organogenesis, by which the optic cup and lens vesicle are formed through a reciprocal invagination of the lens placode and optic vesicle.1 Building on this structural foundation, eye morphogenesis proceeds through the formation of the eye anterior segment using the surface ectoderm, migratory neural crest cells, and undifferentiated cells located at the outer margins of the optic cup. These “late” processes of eye morphogenesis employ the lens as a local “tissue organizer,”2 as these processes are driven by growth factors generated by the lens,3, 4, 5 as well as by other tissues, including the periocular mesenchyme6 and iris.7 Thus, it is important to consider that studies of lens development are not only important for understanding its own formation but are also inseparable from studies of the entire eye morphogenesis.
For embryologists, lens formation has represented an advantageous model system to understand the process of embryological induction for over 100 years. In the past 25 years, a number of developmental geneticists and molecular biologists joined the field to seek better understanding of lens development at the cellular and molecular levels. These studies generated a complex yet incomplete picture of cellular and molecular processes that govern lens formation and differentiation. The unique properties of the ocular lens that are required for its function include transparency, light refraction, and elasticity. These properties originate from a unique internal cellular organization of the lens as well as its status as an avascular, noninnervated, and encapsulated tissue. At the cellular level, the lens comprises a sheet of cuboidal anterior epithelium connected with a mass of highly elongated lens fibers. A hallmark property of these fibers is expression and accumulation of high levels of a relatively small group of water-soluble proteins called lens crystallins. The crystallins are essential for lens transparency and refractive power, and multiple recent studies have shown that they play additional “nonrefractive” roles such as negative regulators of cell death and modulators of autophagy and tissue remodeling. This chapter describes the basic principles of vertebrate lens development in the mouse model with a particular focus on crystallin gene function and expression.
Section snippets
Embryonic Lens Development: Overview
The initial morphological process indicating lens formation is a thickening of the head surface ectoderm to generate lens placodes (Fig. 1), which are comprised of groups of cells with palisade-like morphology. Through a series of morphological movements including the lens placode and the underlying optic vesicle, a three-dimensional (3D) lens primordium is generated in the form of the lens vesicle. Its posterior cells exit the cell cycle and undergo terminal differentiation to an elongated
Cell Cycle Exit, Primary Lens Fiber Cell Differentiation, and Lens Epithelium Differentiation
The lens vesicle is a 3D primordium of the fully formed lens. It has to be precisely positioned within the eyeball to enable proper formation of the optical axis. The lens vesicle is located within the optic cup and behind the nascent anterior segment. Within this arrangement, different parts of the lens vesicle are exposed to different combinations of growth factors that polarize its structure into the anterior or posterior cell compartments. Under the influence of BMPs and fibroblast growth
Conclusions and Future Directions
The long-term goals in the field of embryonic lens development and crystallin regulatory biology include the completion of understanding lens placode formation, as well as subsequent stages of lens morphogenesis within the 3D-space of the embryo. At the cellular level, it will be necessary to comprehend extracellular signaling between the prospective lens cells and other placodal progenitors, and the lens-inducing tissues, such as the “early” (cardiac mesoderm, foregut endoderm, etc.) and the
Acknowledgments
This work was supported by NIH Grants R01 EY012200 (A.C.), EY014237 (A.C.), and EY022645 (W.L.) and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences.
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