Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases

Abstract

SummaryDuring development of the anterior eye segment, cells that originate from the surface epithelium or the neuroepithelium need to interact with mesenchymal cells, which predominantly originate from the neural crest. Failures of proper interaction result in a complex of developmental disorders such Peters' anomaly, Axenfeld-Rieger's syndrome or aniridia. Here we review the role of transcription factors that have been identified to be involved in the coordination of anterior eye development. Among these factors is PAX6, which is active in both epithelial and mesenchymal cells during ocular development, albeit at different doses and times. We propose that PAX6 is a key element that synchronizes the complex interaction of cell types of different origin, which are all needed for proper morphogenesis of the anterior eye. We discuss several molecular mechanisms that might explain the effects of haploinsufficiency of PAX6 and other transcription factors, and the broad variation of the resulting phenotypes.

Niche regulation of corneal epithelial stem cells at the limbus

“…During eye morphogenesis, there is intensive interaction between epithelial and mesenchymal cells to precisely control their proliferation, migration, and differentiation. There are two waves of mesenchymal cell migration involved in the anterior eye development; the first wave cells form the corneal endothelium and stromal keratocytes, and the second differentiates into the trabecular meshwork, the iris stroma and the ciliary body (for review see [110]). Much is to be learned concerning when mesenchymal cells reach the limbal area and how they are destined to form the limbal niche.…”

PAX6 Expression and Retinal Cell Death in a Transgenic Mouse Model for Acute Angle-Closure Glaucoma

“…[1][2][3] Its importance for eye development was demonstrated in several species. The human and murine (small eye) PAX6 protein are identical in their amino acid sequence, and the Drosophila homolog (Eyeless) shows over 90% identity over the paired and the homeodomain.…”

Roles of innervation in developing and regenerating orofacial tissues

“…Cornea development starts shortly after the detachment of the lens vesicle from the surface ectoderm. At this stage, ectomesenchymal cells migrate into the space between the anterior epithelium of the lens vesicle and the surface ectoderm [43]. This mesenchyme progressively condenses to form several layers that are separated by a loose extracellular matrix.…”

“…The posteriorly located mesenchymal cells flatten and form the corneal endothelium. The surface ectoderm forms the corneal epithelium that is separated from the mesenchyme by a thin layer of collagen fibres known as the Bowman's layer [43]. Mesenchymal cells between the corneal endothelium and epithelium differentiate into the highly specialized corneal stromal fibroblasts.…”