BIO380F - Lecture 17 - Development of the Eye: A Series of Inductive Interactions (original) (raw)

Development of the Eye: A Series of Inductive Interactions

Lecture Outline

The Human Eye

The eye is a complex structure and was one of the organs that was experimentally studied by the earliest embryologists. Let's look at the overall structure of the eye and then at it's early embryology. We'll then discuss the control of eye development and some of the information that is known about the differentiation of some of its component cells.

Formation of the Optic Cup

Cross-Sections through head region of embryo revealing changes in optic cup, lens formation and brain:

Three Dimensional representation of how optic cup forms:

Development of the Human Eye

The following events are shown in the series of embryonic cross-sections below (Fig. 14-1. Carlson):

Induction & Lens Development: Early Experiments

The following diagram presents a summary of many different types of experiments that were done first on frog and chick embryos and more recently on mouse embryos. Such experiments have not been performed with human embryos but it is assumed similar results would be found.

Chain of Inductions Mediates Eye Development

These types of tissue transplantation experiments were performed by dozens of different labs over many years. Tissues of various ages and types were combined to reveal the following inductive interactions and results during eye development:

These result are further clarified in the following diagram which presents a summary of a large number of independent experiments by many different researchers. Even before the optic vesicle appears, at least two critical inductive events have occurred. The induction of the neural tube by chordamesoderm defines the anterior regions (diencephalon) where the optic vesicles will form. Endodermal-Mesodermal induction specifies the lens ectoderm which will subsequently be induced by the optic vesicle to become the lens placode.

Subsequent products of the optic vesicle, the optic cup and the future neural retina induce the formation of the choroid & sclera and the lens, respectively. The lens interacts with the future corneal epithelium to induce the outer corneal epithelium which, in turn, induces the neural crest to form the corneal stroma and endoderm. Clearly one stage influences the next resulting in a functional structure in which each of the components is present in the proper position relative to the other eye components.

Sonic Hedgehog & Eye Development

Many factors have been characterized that regulate eye development. For example the transcription factors Six3, Pax6 and Rx1 are expressed at the anterior tip of the neural plate with Pax6 playing a critical role in lens and retina development. Studies on families with congenital eye defects have shown that the absence of Pax6 in humans leads to the complete absence of eyes while other defects are associated with heterozygous conditions (e.g., Glaser et al, 1994. Nature Genetics 7: 463-471). Cyclopia refers to the formation of a single eye in the center of the face. Sonic hedgehog mediates the division of the original single eye field into two. As shown in the following figure, the expression of an eye-specific gene called otx-2 (false red colour) is defective in null sonic hedgehog mutant mouse embryos (Chiange et al, 1996. Nature 383: 407-413).

Wild Type Mouse

Sonic Hedgehog Null Mutant

Notice in the normal mouse, the expression of oxt-2 occurs in the mesencephalon, diencephalon and optic vesicles. In the null hedgehog mutants, the eye fields have not separated and the expression of oxt-2 is seen in the single (cyclopic) optic vesicle plus the brain regions.

Lens Differentiation

Let's take a more detailed look at the structure of the lens before analysing some molecular events underlying it's development.

Differentiation Factors Regulate Lens Cell Differentiation

Some of the factors that regulate lens cell differentiation are being elucidated (Lovicu and McAvoy, 2005. Growth factor regulation of lens development. Developmental Biology 280: 1-14). The following figure summarizes current knowledge.

While the specific factors that underlie the transformation of embryonic ectoderm to presumptive lens ectoderm remain to be identified, FGF and BMP are required for the transformation of presumptive lens ectoderm into the determined cells present in the lens placode. As seen above, the development of the lens placode into the mature lens required the regular division of cells of the lens epithelium that supply the cells that will differentiate into the elongated fiber cells of the lens body. Lens epithelial cell function is maintained by the factors Wnt and Β-catenin. These factors likely function to maintain the cell polarity of the epithelial cells as well as to co-ordinate the cellular rearrangements involved in lens differentiation. The final conversion of lens epithelial cells to lens fiber cells is induced by the further action of FGF and BMP. Slowly we are gaining insight into the factors and signal transduction mechanisms that regulate eye development which in future will guide research into correcting developmental defects in this organ.

Crystallin Protein Expression

Organization of Crystallin Proteins in the Lens: EM Results