The extracellular matrix (ECM) orchestrates tissue morphogenesis during development, providing both mechanical and chemical inputs to cells. Vertebrate eye morphogenesis depends on dynamic and highly coordinated coordinated cell and tissue movements, but how the ECM regulates these processes is still poorly understood. Now, Kristen Kwan and colleagues report a new role for the ECM in the developing eye via a subpopulation of neural crest cells. Using 4D time-lapse imaging, the authors show that neural crest and eye cells are in close proximity throughout optic cup development. In a tfap2a;foxd3 mutant line that almost entirely lacks the neural crest, optic cup morphogenesis is defective, retinal and retinal pigment epithelial (RPE) cells migrate faster and follow abnormal trajectories, and the RPE basement membrane does not form correctly. The ECM component nidogen is expressed by eye-adjacent neural crest cells and is markedly reduced in the RPE basement membranes of the mutants. Dominant-inhibitory forms of nidogen impair optic cup morphogenesis without affecting neural crest migration, while excess wild-type nidogen can partially rescue tfap2a;foxd3 phenotypes. Finally, nidogen crispants phenocopy tfap2a;foxd3 mutants without affecting neural crest migration or survival. Thus, cells of the optic cup require an ECM component secreted from the neural crest to undergo proper morphogenesis.
