Abstract

During vertebrate embryonic development, a population of dorsal neural tube-derived stem cells, termed the neural crest (NC), undergo a series of morphogenetic changes and extensive migration to become a diverse array of cell types. Around the developing eye, this multipotent ocular NC cell population, called the periocular mesenchyme (POM), comprises migratory mesenchymal cells that eventually give rise to many of the elements in the anterior of the eye, such as the cornea, sclera, trabecular meshwork, and iris. Molecular cell biology and genetic analyses of congenital eye diseases have provided important information on the regulation of NC contributions to this area of the eye. Nevertheless, a complete understanding of the NC as a contributor to ocular development remains elusive. In addition, positional information during ocular NC migration and the molecular pathways that regulate end tissue differentiation have yet to be fully elucidated. Further, the clinical challenges of ocular diseases, such as Axenfeld-Rieger syndrome (ARS), Peters anomaly (PA) and primary congenital glaucoma (PCG), strongly suggest the need for better treatments. While several aspects of NC evolution have recently been reviewed, this discussion will consolidate the most recent current knowledge on the specification, migration, and contributions of the NC to ocular development, highlighting the anterior segment and the knowledge obtained from the clinical manifestations of its associated diseases. Ultimately, this knowledge can inform translational discoveries with potential for sorely needed regenerative therapies.

Highlights

  • The neural crest (NC) is an embryonic population of multipotent cells that are extremely important for vertebrate body development

  • NC cells derived from the prosencephalon, mesencephalon, and rhombencephalon comprise the cranial subpopulation that contributes to the frontonasal process, periocular mesenchyme (POM) and pharyngeal arches

  • Cranial NC cells within the POM enter the anterior segment of the eye and form parts of the cornea, iris, sclera, ciliary body, and aqueous outflow pathways (Whikehart, 2010; Cordero et al, 2011; Kish et al, 2011; Williams and Bohnsack, 2015)

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Summary

Frontiers in Cell and Developmental Biology

This multipotent ocular NC cell population, called the periocular mesenchyme (POM), comprises migratory mesenchymal cells that eventually give rise to many of the elements in the anterior of the eye, such as the cornea, sclera, trabecular meshwork, and iris. While several aspects of NC evolution have recently been reviewed, this discussion will consolidate the most recent current knowledge on the specification, migration, and contributions of the NC to ocular development, highlighting the anterior segment and the knowledge obtained from the clinical manifestations of its associated diseases. This knowledge can inform translational discoveries with potential for sorely needed regenerative therapies

INTRODUCTION
CRANIAL NEURAL CREST MIGRATION MEETS OPTIC CUP FORMATION
Dosage Effects
Functional Effects
Findings
FUTURE DIRECTIONS AND CHALLENGES
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