Characterization of DrCol15a1b, a Novel Component of the Stem-Cell Niche in the Zebrafish Retina

There is a clear need to develop novel tools to help improve our understanding of stem-cell biology, and potentially also the utility of stem-cells in regenerative medicine. We report the cloning, functional, and bioinformatic characterization of a novel stem-cell marker in the zebrafish retina, drCol 15a1b. The expression pattern of drCol 15a1b is restricted to stem-cell niches located in the central nervous system, while other collagen XVs are associated with muscle and endothelial tissues. Knocking-down drCol 15a1b expression causes smaller eyes, ear defects, and brain edema. Microscopic analysis reveals enhanced proliferation in the morphant eye, with many mitotic nuclei located in the central retina, together with a delayed differentiation of the mature retinal cell types. Besides, several markers known to be expressed in the CMZ display broader expression areas in morpholino-injected embryos, suggesting an anomalous diffusion of signalling effectors from the shh and notch pathways. These results indicate that drCol 15a1b is a novel stem-cell marker in the central nervous system that has a key role in homing stem-cells into specialized niches in the adult organism. Moreover, mutations in the hCol 18a1 gene are responsible for the Knobloch syndrome, which affects brain and retinal structures, suggesting that drCol 15a1b may function similarly to mammalian Col 18a1. Thus, our results shed new light on the signalling pathways that underlie the maintenance of stem-cells in the adult organism while helping us to understand the role of extracellular matrix proteins in modulating the signals that determine stem-cell differentiation, cell-cycle exit and apoptosis.