The angiopoietin-like factor cornea-derived transcript 6 is a putative morphogen for human cornea

The human cornea-specific protein cornea-derived transcript 6 (CDT6) is a member of the angiopoietin gene family. We report the structural and functional characterization of CDT6. We demonstrate that CDT6 is a secreted protein that folds into disulfide-linked homotetramers by coiled-coil interactions. The finding that CDT6 is expressed at high levels in the avascular corneal stromal layer suggested that the protein, similar to certain angiopoietins, acts as a negative regulator of angiogenesis. To test this hypothesis and to assay the effect of the protein on a growing tissue with high vascular density, CDT6 was expressed in a mouse xenograft model. Expression of CDT6 led to a reduction in tumor growth and aberrant blood vessel formation by inducing massive fibrosis. Interestingly, expression of CDT6 also resulted in the deposition of extracellular matrix components typical for the mature corneal stromal layer. These observations strongly suggest a role as morphogen for CDT6 in inducing a corneal phenotype in vivo.