Formation of corneal endothelium is essential for anterior segment development - a transgenic mouse model of anterior segment dysgenesis

The anterior segment of the vertebrate eye is constructed by proper spatial development of cells derived from the surface ectoderm, which become corne al epithelium and lens, neuroectoderm (posterior iris and ciliary body) and cranial neural crest (corneal stroma, corneal endothelium and anterior iri s). Although coordinated interactions between these different cell types ar e presumed to be essential for proper spatial positioning and differentiati on, the requisite intercellular signals remain undefined. We have generated transgenic mice that express either transforming growth factor alpha (TGF alpha) or epidermal growth factor (EGF) in the ocular lens using the mouse alpha A-crystallin promoter. Expression of either growth factor alters the normal developmental fate of the innermost corneal mesenchymal cells so tha t these cells often fail to differentiate into corneal endothelial cells. B oth sets of transgenic mice subsequently manifest multiple anterior segment defects, including attachment of the iris and lens to the cornea, a reduct ion in the thickness of the corneal epithelium, corneal opacity, and modest disorganization in the corneal stroma. Our data suggest that formation of a corneal endothelium during early ocular morphogenesis is required to prev ent attachment of the lens and iris to the corneal stroma, therefore permit ting the normal formation of the anterior segment.