Pax2a, but not pax2b, influences cell survival and periocular mesenchyme localization to facilitate zebrafish optic fissure closure

Abstract

Background: Pax2 is required for optic fissure development in many organisms, including humans and zebrafish. Zebrafish loss-of-function mutations in pax2a display coloboma, yet the etiology of the morphogenetic defects is unclear. Further, pax2 is duplicated in zebrafish, and a role for pax2b in optic fissure development has not been examined. Results: Using a combination of imaging and molecular genetics, we interrogated a potential role for pax2b and examined how loss of pax2 affects optic fissure development. Although optic fissure formation appears normal in pax2 mutants, an endothelial-specific subset of periocular mesenchyme (POM) fails to initially localize within the optic fissure, yet both neural crest and endothelial-derived POM ectopically accumulate at later stages in pax2a and pax2a; pax2b mutants. Apoptosis is not up-regulated within the optic fissure in pax2 mutants, yet cell death is increased in tissues outside of the optic fissure, and when apoptosis is inhibited, coloboma is partially rescued. In contrast to pax2a, loss of pax2b does not appear to affect optic fissure morphogenesis. Conclusions: Our results suggest that pax2a, but not pax2b, supports cell survival outside of the optic fissure and POM abundance within it to facilitate optic fissure closure.

Loss of zebrafish dzip1 results in inappropriate recruitment of periocular mesenchyme to the optic fissure and ocular coloboma

“…In contrast, the neural crest, an extraocular cell population implicated in optic fissure basement membrane breakdown and closure [ 15 , 65 – 68 , 70 ], is not appropriately recruited to the optic fissure in dzip1 mutants ( Fig 6 ). Even though neural crest cells do not arrive at the appropriate time, at later timepoints, they do accumulate to a greater extent in dzip1 mutants compared to wild type siblings, a finding observed in at least one other coloboma model with an optic fissure closure defect [ 80 ]. This suggests that even once the cells arrive at the optic fissure, they may not be able to execute their appropriate function in basement membrane breakdown.…”