During eye morphogenesis, the optic vesicle invaginates to give rise to the optic cup. This process creates a transient opening, termed the optic fissure, which eventually closes as development proceeds. Failure in optic fissure closure (OFC) is known to cause ocular coloboma, leading to partial or complete blindness, yet the mechanisms underlying this closure event remain poorly understood. Here, Jane Sowden and co-workers investigate how and when OFC occurs in the human eye. Their histological analyses of human embryonic eyes reveal that OFC occurs during days 41-44 of development, progressing bi-directionally from a closure initiation midpoint. Using laser capture microdissection of human and mouse embryos, followed by RNA-sequencing, the authors identify novel genes as well as coloboma-associated genes that are enriched in OFC margins. They also report that genes involved in epithelial-to-mesenchymal transition (EMT) are expressed in these margins. Accordingly, cells within the optic fissure display changes in morphology consistent with EMT; they delaminate, exhibit transient loss of cell polarity, and extend cytoplasmic protrusions that appear to interact with cells from the opposing margin. Based on their findings, the authors propose that cells at fissure margins undergo transient EMT to facilitate the cell rearrangements that allow formation of the eye globe structure.
