Systems biology of lens development: A paradigm for disease gene discovery in the eye

摘要: Over the past several decades, biology of developing lens has been investigated using molecular genetics-based approaches in various vertebrate model systems. These efforts, involving target gene knockouts or knockdowns, have led to major advances our understanding morphogenesis and pathological basis cataracts, as well other related eye defects. In particular, we now a functional regulators such Pax6, Six3, Sox2, Oct1 (Pou2f1), Meis1, Pnox1, Zeb2 (Sip1), Mab21l1, Foxe3, Tfap2a (Ap2-alpha), Pitx3, Sox11, Prox1, Sox1, c-Maf, Mafg, Mafk, Hsf4, Fgfrs, Bmp7, Tdrd7 this tissue. However, whether these individual interact their targets overlap, significance interactions during morphogenesis, is not defined. The arrival high-throughput for expression profiling (microarrays, RNA-sequencing (RNA-seq), etc.), which can be coupled with chromatin immunoprecipitation (ChIP) RNA (RIP) assays, along improved computational resources publically available datasets (e.g. those containing comprehensive protein-protein, protein-DNA information), presents new opportunities advance tissue on global systems level. Such systems-level knowledge will lead derivation underlying regulatory network (GRN), defined circuit map regulator-target development, applied expedite cataract discovery. review, cover microarrays, RNA-seq, ChIP that are already being studies discuss strategies assembling interpreting vast amounts information effective dispersion scientific community. interpretation context rich obtained through application traditional single-gene focused experiments lens. Finally, vision integrating diverse single web-based user-friendly tool iSyTE (integrated Systems Tool Eye discovery) - resource proving identification characterization genes linked development cataract. We anticipate similar approach ocular tissues retina cornea, even organ systems, significantly impact disease