Morphogenetic and patterning defects explain the coloboma phenotype of the eye in the Mexican cavefish

The morphogenesis of the vertebrate eye consists of a complex choreography of cell movements, tightly coupled to axial regionalization and cell type specification processes. Any disturbance in these events can lead to developmental defects and blindness. Here we have deciphered the sequence of defective events leading to coloboma phenotype in the embryonic eye of the blind cavefish of the species Astyanax mexicanus. Using comparative live imaging on targeted enhancer-trap Zic1:hsp70:GFP reporter lines of both the normal, river-dwelling morph and the cave morph of the species, we identified major defects in initial optic vesicle size and optic cup invagination in cavefish. Combining these results with gene expression analyses, we also discovered defects in axial patterning affecting mainly the temporal retina, in optic stalk tissue specification, and in the spreading processes involving the retinal pigmented epithelium cells. Based on these results, we propose a developmental scenario to explain the cavefish phenotype and discuss developmental constraints to morphological evolution. The cavefish eye appears as an outstanding natural mutant model to study molecular and cellular processes involved in optic region morphogenesis.