Dcbld2 is Essential in Zebrafish Retinal Development

DCBLD2 is a type 1 transmembrane receptor that is expressed throughout the nervous system. Its structure resembles Neuropilins, which are co-receptors for the Semaphorin (Sema) family of repulsive guidance cues. Furthermore, DCBLD2 can bind to Sema4B and thus has features that suggest it could influence neuronal positioning and/or angiogenesis during development. Additionally, high DCBLD2 expression is linked to many forms of cancer, including glioma, neuroendocrine, lung and pancreatic cancer. While a role for DCBLD2 in angiogenesis has been described using morphant zebrafish, its function in the nervous system has yet to be elucidated. We determined that dcbld2 is expressed in the developing zebrafish visual system. We next disrupted dcbld2 expression using three approaches: (i) a slice-blocking morpholino (ii) CRISPR interference and (iii) a zebrafish mutant producing an aberrant Dcbld2 protein that truncates the protein in the ectodomain just prior to the transmembrane domain. In each approach retinal defects were observed. However, observed phenotypes were observed at different stages, to differing degrees, and in some cases unique to one disruption method. The data are discussed towards a model integrating the observations and leading to a better understanding of Dcbld2 function during eye development