The eye as an organizer of craniofacial development

Abstract

The formation and invagination of the optic stalk coincides with the migration of cranial neural crest (CNC) cells, and a growing body of data reveals that the optic stalk and CNC cells communicate to lay the foundations for periocular and craniofacial development. Following migration, the interaction between the developing eye and surrounding periocular mesenchyme (POM) continues, leading to induction of transcriptional regulatory cascades that regulate craniofacial morphogenesis. Studies in chick, mice, and zebrafish have revealed a remarkable level of genetic and mechanistic conservation, affirming the power of each animal model to shed light on the broader morphogenic process. This review will focus on the role of the developing eye in orchestrating craniofacial morphogenesis, utilizing morphogenic gradients, paracrine signaling, and transcriptional regulatory cascades to establish an evolutionarily-conserved facial architecture. We propose that in addition to the forebrain, the eye functions during early craniofacial morphogenesis as a key organizer of facial development, independent of its role in vision.

Figure 1. The dark-adapted lower Congo River blind spiny eel, Mastacembelus brichardi, preserves its eyes behind a protective cover

Upper panel: image of the adult eel (markings in 1mm increments). Lower panel: Hematoxylin and eosin stain of a frontal section through the eel head. Arrows point to the eyes. Note the juvenile appearance of the eyes in this adult specimen. (Courtesy of the Comparative Ocular Pathology Laboratory of Wisconsin, Richard R. Dubielzig, DVM, ACVP, and Charles Schobert, DVM, MS. The American Museum of Natural History Congo River Project is led by Dr. Melanie Stiassny, Department of Ichthyology, AMNH, New York, NY).

Figure 2. Spatial morphogen and gene expression pathways

Upper panel: Hox expression zones in early embryogenesis with migration paths for the CNC cells. Lower panel: morphogen synthesis occurring in primordial eye tissues, but the receptors and activated pathways reside in the surrounding POM. Large arrows reflect different potential streams of Shh and Ihh morphogenic gradients, one from the forebrain, and the other from the eye.