Cellular and Molecular Dynamics of Vertebrate Eye Morphogenesis: How Neural Crest Shapes the Embryonic Eye
Authors: Kwan Kristen M. , Bryan Chase D. , Casey Macaulie A. 
Published: June 2021

Precise and stereotyped 3‐dimensional tissue structure, established during the process of morphogenesis, is essential for proper organ function. In the visual system, aberrant structural development of the embryonic eye can lead to visual impairment and blindness. Despite increasing knowledge of pathways controlling the differentiation of many cell types in the eye, we still lack a basic understanding of the mechanisms controlling its morphogenesis. Using a combination of 4‐dimensional timelapse imaging, computational approaches, and zebrafish genetics, we seek to unravel the cellular and molecular basis, including both intrinsic and extrinsic cues, for the morphogenesis of the initial embryonic eye structure, the optic cup. One particular extrinsic cell population of interest is the neural crest: migratory mesenchymal cells are essential for the development and morphogenesis of many epithelial organs. In mouse, eye defects have been described in a neural crest mutant, but the mechanisms underlying aberrant optic cup development are unknown. Using zebrafish, we asked when and how neural crest contacts the developing eye, and how optic cup defects arise.

We find that at the earliest stages of optic vesicle formation, neural crest cells are in contact with the optic vesicle; by the end of optic cup morphogenesis, these neural crest derived cells encapsulate the optic stalk and optic cup, except for its distal, lens‐facing side. To test the role of neural crest, we utilize the zebrafish tfap2ats213;foxd3zdf10 double mutant: in the absence of neural crest, optic cup invagination is defective, and using 4D cell tracking, we pinpointed the cell movements disrupted by loss of neural crest.

What molecule is neural crest providing to control optic cup morphogenesis? Strikingly, using electron microscopy, we directly observe loss of basement membrane assembly in the neural crest mutant. Nidogen, a laminin‐collagen crosslinking protein expressed by neural crest and essential for optic cup morphogenesis in embryonic stem cells, appears to be a crucial factor: dominant negative nidogen disrupts wild type optic cup morphogenesis without affecting neural crest migration, and overexpression of wild type nidogen partially rescues optic cup morphogenesis in neural crest mutants. There are four nidogen genes in zebrafish (nid1a, nid1b, nid2a, and nid2b), and we are now generating quadruple mutants to examine loss‐of‐function phenotypes.

Our data suggest that neural crest provides crucial extracellular matrix factors to regulate optic cup morphogenesis, and highlight diverse roles mesenchyme can play in epithelial organ development and morphogenesis.

Support or Funding Information

NIH/NEI R01EY025378, R01EY025780 to KMK. CDB was supported by the University of Utah T32 Developmental Biology Training Grant (NIH T32HD007491).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.