Canopy1, a novel positive-feedback regulator of FGF signaling around the
midbrain-hindbrain boundary in zebrafish
The midbrain-hindbrain boundary (MHB, isthmus) mediates the induction of tectal and
cerebellar formation via release of Fibroblast growth factor 8 (FGF8). By means of a
combined method of Ordered Differential Display and expression screening to search for downstream genes of a transcription factor, Islet-3, we identified Canopy1 (Cnpy1), a novel MHB-specific, ER-resident, saposin-related protein. Among Canopy family proteins, only Cnpy1 is specifically expressed in the MHB of zebrafish embryos. Cnpy1 is essential for and induced by FGF signaling and this interplay is pivotal in tectal and cerebellar development. Together with other FGF signaling components, Cnpy1 contributes to a positive-feedback loop of FGF signaling in the MHB, enabling the MHB to exert its role as an organizer for the tectal and cerebellar development.