Identification of lens-regulated genes driving anterior eye development and eye size.

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 regulation of eye development by the lens, we performed transcriptome analysis of lens-removed and contralateral unoperated embryonic chicken eyes. Lens-regulated genes implicated in periocular mesenchyme, cornea and anterior optic cup development were identified. Identified candidates included genes known to be regulated by lens-derived signals and important for anterior eye development, including WNT pathway genes. Factors not previously implicated in eye development also were identified, paving the way for additional research in this area. 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. Intriguingly, transcriptomic differences were identified in retinas from male versus female chicken embryos, suggesting sexual dimorphism from early stages. These analyses have identified candidate genes and biological pathways involved in eye development, providing avenues for new research in this area. RNA-seq profiling of operated and contralateral unoperated embryonic chicken retinas 6 hours after lens removal from one eye at Hamburger and Hamilton (HH) 23 (~E4).