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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, whereas 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 ciliary marginal zone display broader expression areas in morpholino‐injected embryos, suggesting an anomalous diffusion of signaling effectors from the sonic hedgehog 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 signaling 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. S TEM  C ELLS  2010;28:1399–1411

Characterization of drCol 15a1b : A Novel Component of the Stem Cell Niche in the Zebrafish Retina