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Bone morphogenetic protein 7 (BMP7) belongs to the transforming growth factor β (TGF-β) family, which not only induces cartilage and bone formation, but also regulates eye development and melanoma tumorigenesis in mammals. In teleosts, BMP7 differentiates into two subtypes,  bmp7a  and  bmp7b , which have clearly differentiated structures. To fully understand the functional differentiation of  bmp7a  and  bmp7b  in fish species, we successfully constructed  bmp7a  and  bmp7b  gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that  bmp7a  mutation caused abnormal development of the embryo’s dorsal-ventral pattern that led to death;  bmp7b  mutation induced growth inhibition and increased melanin production in the skin and eye of mutants. Histological analysis revealed that melanin in the retina of the eyes in  bmp7b  mutants increased, and behavioral observation showed that the vision and sensitivity to food of the mutants were reduced. Transcriptome analysis of the skin and eye tissues showed that the expression changes of  wnt7ba  and  gna14  in  bmp7b  mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in  bmp7b  mutants led to defects in phototransduction, and seven DEGs ( rgs9a ,  rgs9b ,  rcvrn2 ,  guca1d ,  grk1b ,  opn1mw4,  and  gc2 ) were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of  bmp7a  and  bmp7b  in teleosts and the first report about the inhibitory effect of  bmp7b  on melanogenesis may provide useful information for the future research on human melanoma-related diseases.

Functional Differentiation of BMP7 Genes in Zebrafish: bmp7a for Dorsal-Ventral Pattern and bmp7b for Melanin Synthesis and Eye Development