Our observations that upregulated Wnt/β-catenin signaling associates with coloboma formation seem to be at odds with the fact that a coloboma phenotype is also observed in cases when the Wnt/β-catenin signaling is reduced, as in the case of humans with mutations in the Wnt receptor gene FZD5 (Liu et al., 2016) and Fzd5−/− null mice, which show increased apoptosis and increased Pax2 expression in the OC (Liu and Nathans, 2008). The gene discussed is PAX2; the disease is coloboma.