The vertebrate eye begins as a bulge in the embryonic neural tube, and it one of the first identifiable parts of the embryonic nervous system. As development proceeds, additional tissues contribute and are coordinated in order to form the adult eye. This includes the surface ectoderm, which forms the lens and cornea. The cranial neural crest, an important embryonic "tissue" also contributes heavily to the eye, and among other things, contributes the stroma of the cornea and iris, and forms the sclera, choroid, and ocular muscles.

The interaction between these tissues controls the formation and size of the eye and the type of tissue that differentiates from the optic neuroepithelium. The neuroepithelium of the eye is a portion of the embryonic brain and maintains a direct connection to the brain through the optic nerve. Within the optic cup this neuroepithelium differentiates into a totally unique neural tissue- the neural retina. Yet it also differentiates into three other essential tissues. In the back of the eye, the outer layer of the optic cup differentiates into the pigmented epithelium, a simple cuboidal epithelium that is essential for photoreceptor survival. In the front of the eye, the bilayer combines with neural crest and differentiates into the iris in front of the lens and into the ciliary epithelium behind. The iris is a muscular diaphragm that controls the amount of light let into the eye and the ciliary body secretes the aqueous humor fluid that keeps the eye inflated and supports the lens and cornea.

The field of eye development has entered an extremely rich phase, with the identification of eye specific genetic cascades that function across species. However, after years of study, it is still not possible to definitively understand how these transcription factors produce an eye. Work in the lab does not address the role of any specific transcription factor, but rather looks at the inductive interactions that presumptive eye tissues engage in, and how the interactions influence the placement and the quantity of the particular tissues of the optic cup.

Current projects center on…

1-The specification of the neural retinal portion of the optic anlage.
The specification of the neural retina is dependent on tissue-tissue communication. Growth factors mediate communication between tissues. Wnt, BMP and Hedgehog signals have all been identified in the eye, with various effects. FGF signaling is involved in the specification and placement of the neural retina in vivo. Interestingly, the eyes of mice that are doubly mutant for the two major FGFs expressed in the early embryo develop normal eyes. Current work aims to determine if additional FGFs are present, or if a parallel mechanism is present to compensate for the loss of FGF signaling.

2-The morphogenetic movements that turn the optic tissue from a vesicle into a cup.
The morphogenetic movements that turn the optic tissue from a vesicle into a cup are dependent on signals coming from the surface ectoderm-as defined experimentally. A potential signal for the induction of optic cup morphogenesis is being defined and studied in the lab. It differs from previous interpretations in that the potential signal seems to be active prior to the formation of the lens.

3-The development of the ciliary body and iris.
In the anterior of the optic cup, the neuroepithelium and associated neural crest cells differentiate into secretory (ciliary body) and muscular (iris) organs. The current view is that these specialized tissues are organized by the lens, but novel findings in the lab show that they may specified much earlier, at optic vesicle stages. As almost nothing is known about the development of the ciliary body, the iris, or the tissues of the anterior chamber angle, this work will give new insight into the formation of these essential tissues. We hope that by understanding the requirements for the normal formation of tissues both in the anterior of the eye, such as the ciliary body and the anterior angle (Schlemm's canal and the trabecular meshwork) it will give us insight into developmental syndromes such as Reigers syndrome, and diseases such as glaucoma.

The lab uses the chick embryo as a model system, as it is well suited to embryological study, with a well studied, accessible and impressive embryonic visual system. The model is amenable to viral mediated gene transfer, microsurgery and transplantation. The chicken genome is near to being completely sequenced and this will substantially increase our ability to move seamlessly between organisms to better understand the essential aspects of the genetics of eye development and tissue communication.