Identification of lens-regulated genes driving anterior eye development

Signals from the lens regulate multiple aspects of eye development, including establishment of eye size, patterning of the presumptive iris and ciliary body in the anterior optic cup and migration and differentiation of neural crest cells. To advance understanding of the molecular mechanism by which the lens regulates eye development, we performed transcriptome profiling of embryonic chicken retinas after lens removal. Genes associated with nervous system development were upregulated in lens-removed eyes, but the presumptive ciliary body and iris region did not adopt a neural retina identity following lens removal. Lens-regulated genes implicated in periocular mesenchyme, cornea and anterior optic cup development were identified, including factors not previously implicated in eye development. Unexpectedly, transcriptomic differences were identified in retinas from male versus female chicken embryos, suggesting sexual dimorphism from early stages. In situ hybridisation of embryonic chicken eyes and analyses of datasets from embryonic mouse and adult human eyes confirmed expression of candidate genes, including multiple WNT genes, in tissues important for anterior eye development and function. Remarkably, pharmacological activation of canonical WNT signalling restored eye development and size in the absence of the lens. These analyses have identified candidate genes and biological pathways involved in eye development, providing avenues for new research in this area.