Dcbld2/esdn Is Essential For Proper Optic Tract Formation And Retinal Lamination

ABSTRACT The Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2/ESDN/CLCP1) is a type-I, transmembrane receptor that mediates diverse cellular processes such as angiogenesis, vascular remodeling, cellular migration and proliferation. Identification of DCBLD2 in a proteomics screen to identify substrates of Src family tyrosine kinases that bind the Src homology 2 domain of CT10 regulator of kinase-Like (CrkL), a critical scaffolding protein for neuronal development, led to a need for further characterization of the protein. To elucidate the role of this interaction and potential novel function of DCBLD2, an in vivo approach utilizing Danio rerio (zebrafish) was conducted. dcbld2 was found localized in neuronal tissues during development, with strong expression in the retina. Knockdown of the protein led to a deficiency of retinal ganglion cells and the optic tracts, or nerve bundles, they project to innervate the brain. Serial sections revealed malformation of the normally discrete layering of retinal cell types, and smaller eye area overall. These findings suggest a role for dcbld2 in developing nervous tissue, specifically neuronal migration during interkinetic nuclear migration. While it is has been shown that dcbld2 has a role in the developmental patterning of intersegmental vessels in the tail of zebrafish, the protein has not been investigated in the context of neurogenesis. The loss of RGCs and lamination defects observed in the eye, along with its association with the CrkL-SH2 domain, implicate it in processes that allow for the proper differentiation of neurons. This study has brought us further down the path to understanding the multiple functions of the receptor; however, further studies are required to delineate the exact mechanistic function of the dcbld2 receptor