Functional Analysis of Protease ADAMTS 6 during Vertebrate Eye Formation

Extracellular matrix (ECM) remodeling and epithelial sheet fusion occur during the development of many different tissues, including the vertebrate eye (Lu et al., 2011) (Pai et al., 2012). During morphogenesis of the eye, the ventral hemisphere of the developing retinal tissue forms an opening called the optic fissure which must undergo epithelial fusion (Pai et al., 2012). Failure of optic fissure fusion leads to a congenital blinding disorder called coloboma (Gregory-Evans, 2004). A long standing question pertaining to the mechanism of optic fissure fusion is exactly which ECM remodeling enzymes are actively involved in dismantling the ECM to allow for fusion to occur. I hypothesize that ADAMTS 6 has some function in the fusion of the optic fissure. The expression pattern of ADAMTS 6 was characterized to determine whether it has the spatiotemporal capacity to act as an ECM remodeler for epithelial sheet fusion. Through use of RNA in situ hybridization, the expression of ADAMTS 6 was compared at chronological time points in the development of zebrafish embryos. Findings seem to contradict previous work in the lab that suggested ADAMTS 6 has little to no function in the optic fissure during fusion of the retina (Taylor et al., 2017). The comparison of ADAMTS 6’s expression pattern in wildtype and Pax2noi mutant embryos at certain time points had previously showed no changes in the optic fissure suggesting that there was no function (Taylor et al., 2017). However, optic fissure fusion of embryos injected with mRNA producing protein overexpression appears to be disrupted. Deeper analysis with different tests will need to be performed to determine the how of this mechanism