Development of neural crest cells: and contribution to corneal endothelium

Abstract

Neural crest cells are an early embryonic cell population characterised by their multipotency and high migratory capacity. In addition to contributing to various facial and bodily tissues, including bone and cartilage, neural crest cells play a key role in corneal development by giving rise to periocular mesenchyme. Periocular mesenchyme further differentiates to corneal endothelial cells, which are vital for maintaining corneal function. Corneal endothelial cells preserve corneal transparency by actively pumping excess fluid out of the stroma. Since the cells have limited proliferative capacity in vivo, damage to corneal endothelium is typically irreversible and can lead to loss of vision. Aim of this thesis is to reveal some of the mechanisms and signalling factors underlying the development of neural crest cells and their differentiation to corneal endothelial cells. The development of neural crest cells is tightly linked to neurulation, during which neural crest cells are specified from the neural plate border. A gene regulatory network plays a role in the induction and regulation of different stages of development, including induction of neural plate border, specification of neural crest, delamination through epithelial to mesenchymal transition, migration and differentiation to specific cell types. During delamination and epithelial to mesenchymal transition, neural crest cells undergo morphological changes that allow them to detach neural tube and migrate to their target locations. In context of corneal endothelium development, neural crest cells migrate to the ocular region where they differentiate via periocular mesenchyme to corneal endothelial cells. This differentiation is controlled by the signalling cues received both during migration and after arrival. Signalling factors, including retinoic acid and transforming growth factor-beta activate intrinsic signalling pathways that drive corneal endothelium differentiation. Understanding the mechanisms behind neural crest cells development to corneal endothelial cells could provide new insights for improving in vitro differentiation protocols of corneal endothelial cells. These could further be utilized in cell-based therapies for corneal endothelium dysfunction.