Image courtesy of Joachim Wittbrodt, European Molecular Biology Laboratory, Heidelberg, Germany

Eye development in vertebrates takes place during late gastrulation and starts with the specification of retinal precursor cells (RPCs). Subsequently, the evagination of optic vesicles from either side of the embryonic forebrain, leads to the formation of the optic nerve and retina. Using in vivo imaging techniques in the Japanese ricefish medaka, Rembold et al. now show that rx3-dependent individual cell movements, rather than sheets of tissue, drive optic vesicle evagination.

To track individual RPC movement during eye morphogenesis, the authors generated embryos expressing GFP specifically in RPCs and their descendents (rx3::GFP) and injected them with histone H2B–mRFP mRNA, which stains all nuclei. As expected, they found RPCs to localize within the eye field in the anterior neural plate. Using confocal time-lapse microscopy, they show how the eye field condenses to a single domain in the forebrain and that optic vesicle evagination takes place as the neural keel, presumptive central nervous system, is still forming.

By simultaneously tracking several hundred cells, Rembold et al. were able to reconstruct the movements of individual cells during optic vesicle evagination. Whereas ventromedial RPCs remained stationary, keeping the eye field wide during evagination, both lateral RPCs and prospective prosencephalic cells migrated towards the midline. As they approached the midline, RPCs from the lateral eye field moved ventrally and then laterally into the evaginating vesicle. Analyses of the rx3 mutant eyeless revealed that in the absence of rx3 all RPCs move towards the midline and localize within the neural tube therefore, failing to evaginate. Lateral RPCs adopt the shape and behaviour of neuroepithelial cells, indicating that rx3 confers migratory properties to RPCs that distinguish them from surrounding forebrain cells.

Intriguingly, wild-type RPCs transplanted into rx3 mutant embryos migrated normally and were able to rescue optic vesicle evagination in a cell-autonomous manner. These cells moved in small groups or on their own, as single cells, through the mutant tissue to establish optic vesicles, confirming that rx3 is required to induce RPC migration. Despite the fact that the cues directing this migration are still to be established, they seem to be unaffected in the eyeless mutant.

Time-lapse movies show that single migrating RPCs exchange neighbours as they move from the eye field into optic vesicles demonstrating that individual cells, rather than sheets or groups of them, contribute to eye morphogenesis. It will be interesting to examine whether this is also the case in other organs.

Author: Monica Hoyos-Flight