Corneal development: Role of the periocular mesenchyme and bi-directional signaling

The cornea is a highly specialized transparent tissue located at the anterior most surface of the eye. It consists of three main layers, the outer stratified squamous epithelium, the inner endothelium, and the intermediate stroma. Formation of these layers during development involves a complex interaction between ectodermal-derived structures, such as the overlying head ectoderm with the periocular mesenchyme (POM), the latter of which is comprised of neural crest cells (NCC) and mesoderm-derived progenitor cells. Regulation of corneal epithelial development, including both epithelial cell fate and stratification, has been shown to depend on numerous bi-directional mesenchymal-epithelial signaling pathways. In this review we pay particular attention to the genes and signaling pathways that involve the POM. •Corneal development depends on bi-directional signaling between the overlying head ectoderm and the periocular mesenchyme (POM).•The POM is comprised of neural crest cells (NCC) and mesoderm derived progenitor cells.•Regulation of corneal epithelial cell fate and stratification has been shown to depend on numerous bi-directional mesenchymal-epithelial signaling pathways.•Key signaling pathways involved in corneal development include Wnt/β-catenin, Retinoic Acid, TGFβ, and FGF.•Key transcription factors controlling corneal development include Pitx2, Foxc1, Pax6 and AP-2β.