Neural crest derivatives in ocular development: Discerning the eye of the storm

Abstract

Neural crest cells (NCCs) are vertebrate-specific transient, multipotent, migratory stem cells that play a crucial role in many aspects of embryonic development. These cells emerge from the dorsal neural tube and subsequently migrate to different regions of the body, contributing to the formation of diverse cell lineages and structures, including much of the peripheral nervous system, craniofacial skeleton, smooth muscle, skin pigmentation, and multiple ocular and periocular structures. Indeed, abnormalities in neural crest development cause craniofacial defects and ocular anomalies, such as Axenfeld-Rieger Syndrome and primary congenital glaucoma. Thus, understanding the molecular regulation of neural crest development is important to enhance our knowledge of the basis for congenital eye diseases, reflecting the contributions of these progenitors to multiple cell lineages. Particularly, understanding the underpinnings of NC formation will help to discern the complexities of eye development, as these NCCs are involved in every aspect of this process. In this review, we summarize the role of ocular NCCs in eye development, particularly focusing on congenital eye diseases associated with anterior segment defects and the interplay between three prominent molecules, Pitx2, Cyp1b1, and RA, which act in concert to specify a population of neural crest-derived mesenchymal progenitors for migration and differentiation, to give rise to distinct anterior segment tissues. We also describe recent findings implicating this stem cell population in ocular coloboma formation, and introduce recent evidence suggesting the involvement of NCCs in optic fissure closure and vascular angiogenesis.

The hyaloid vasculature facilitates basement membrane breakdown during choroid fissure closure in the zebrafish eye

“…As discussed above, TEM studies in mouse have shown that BM breakdown correlates with a population of cells that are possibly mesenchymal in origin (Hero, 1990; Hero et al, 1991). POM cells, comprised of lateral plate mesenchyme and cranial neural crest derivatives, migrate into the developing eye to form a variety of ocular and extraocular structures (Gage et al, 2005; Williams and Bohnsack, 2015). POM cells are known to be required for CFC, with defects in lmx1b , Tfap2a / tfap2a, foxc1 , nlz1 and Pitx2 / pitx2 resulting in colobomas (Gage et al, 1999; Brown et al, 2009; Gestri et al, 2009; McMahon et al, 2009; Bassett et al, 2010; Lupo et al, 2011).…”

What's retinoic acid got to do with it? Retinoic acid regulation of the neural crest in craniofacial and ocular development

“…Cranial neural crest cells that delaminate from the posterior mesencephalon and rhombencephalon give rise to the cartilage and bones of the midface, middle ear, jaw, and neck (Figure 1a,b,d). Neural crest cells from the rhombencephalon, which are organized into seven separate rhombomeres, migrate into the corresponding first through fourth pharyngeal arches and ultimately develop into the mandible, teeth, middle ear, and hyoid (Barembaum & Bronner-Fraser, 2005;Gong, 2014;Hong & Saint-Jeannet, 2005;Minoux & Rijli, 2010;Steventon, Carona-Fontaine, & Mayor, 2005;Trainor, 2005;Williams & Bohnsack, 2015). Neural crest cells from the rhombencephalon, which are organized into seven separate rhombomeres, migrate into the corresponding first through fourth pharyngeal arches and ultimately develop into the mandible, teeth, middle ear, and hyoid (Barembaum & Bronner-Fraser, 2005;Gong, 2014;Hong & Saint-Jeannet, 2005;Minoux & Rijli, 2010;Steventon, Carona-Fontaine, & Mayor, 2005;Trainor, 2005;Williams & Bohnsack, 2015).…”

Directed Differentiation of Human Corneal Endothelial Cells From Human Embryonic Stem Cells by Using Cell-Conditioned Culture Media

“…29,31 Studies have shown that PITX2 could be detected in POMPs progenitor for CECs, and that POMPs has a regulatory role in the development of corneal stroma, sclera, and ocular vessels. 17 Taken together, FOXC1 and PITX2 can serve as markers for POMPs. The results showed that expression of FOXC1 and PITX2 increased significantly at the first day after HCSC-CM induction, peaked at the third day, and then decreased gradually ( Fig.…”

“…17,18 In related research, mouse PA6 fibroblasts were co-cultured with hESCs to induce differentiation toward stromal keratocytes 19 ; however, the mechanisms governing human NC cell differentiation to CECs remains unclear. During cornea development in the embryonic stage, the microenvironment surrounding the migrated NC cells determines the ultimate fate of CECs, including human corneal stromal cells (HCSC) and human lens epithelial cells (HLEC).…”

“…During cornea development in the embryonic stage, the microenvironment surrounding the migrated NC cells determines the ultimate fate of CECs, including human corneal stromal cells (HCSC) and human lens epithelial cells (HLEC). 17,20 In this in vitro study, we tried to mimic the in vivo microenvironment of corneal development by using conditioned medium containing HLECs, HCSC, and human corneal endothelial cells (HCEC). To validate the effectiveness of the co-culture system, a two-step approach of induction from hESCs to HCEC was established.…”