The Ocular Neural Crest: Specification, Migration, and Then What?

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.

Loss of zebrafish dzip1 results in inappropriate recruitment of periocular mesenchyme to the optic fissure and ocular coloboma

“…We next considered potential underlying causes of impaired basement membrane breakdown and disrupted optic fissure closure. The periocular mesenchyme (POM) is a heterogeneous extraocular migratory cell population comprised of neural crest and also mesodermally-derived migratory cells [ 63 , 64 ]. The POM has been implicated in optic fissure closure [ 15 , 65 – 68 ]: electron microscopy revealed POM cells near sites where basement membrane breakdown were taking place and transplanting the eye to sites distant from POM led to failure of optic fissure closure [ 11 , 14 , 69 ].…”

Zebrafish models of alx-linked frontonasal dysplasia reveal a role for Alx1 and Alx3 in the anterior segment and vasculature of the developing eye

“…Neural crest that populates the anterior segment is highly heterogenous; its influence on retinal development during embryogenesis is poorly understood and likely to vary across vertebrates ( Takamiya et al, 2020 ; Van Der Meulen et al, 2020 ; Williams and Bohnsack, 2015 , 2020 ). It is also likely that the ocular anterior segment offers differing degrees of protection to the developing retina in humans versus lower vertebrates.…”

A Fetus with Congenital Microcephaly, Microphthalmia and Cataract Was Detected with Biallelic Variants in the OCLN Gene: A Case Report

“…Increasing numbers of genetic changes associated with both syndromic and isolated microphthalmia have been reported [ 27 ]. Recently, studies suggest that the disruption of signaling in neural crest cells can lead to alterations in neural epithelial derived optic cup formation, resulting in microphthalmia [ 28 , 29 ]. TJ proteins, especially those with MARVEL (MAL and related proteins for vesicle traffic and membrane link) domain are usually regulators or components of many important signaling pathway.…”