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

Abstract

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, <i>bmp7a</i> and <i>bmp7b</i>, which have clearly differentiated structures. To fully understand the functional differentiation of <i>bmp7a</i> and <i>bmp7b</i> in fish species, we successfully constructed <i>bmp7a</i> and <i>bmp7b</i> gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that <i>bmp7a</i> mutation caused abnormal development of the embryo's dorsal-ventral pattern that led to death; <i>bmp7b</i> 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 <i>bmp7b</i> 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 <i>wnt7ba</i> and <i>gna14</i> in <i>bmp7b</i> mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in <i>bmp7b</i> mutants led to defects in phototransduction, and seven DEGs (<i>rgs9a</i>, <i>rgs9b</i>, <i>rcvrn2</i>, <i>guca1d</i>, <i>grk1b</i>, <i>opn1mw4,</i> and <i>gc2</i>) were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of <i>bmp7a</i> and <i>bmp7b</i> in teleosts and the first report about the inhibitory effect of <i>bmp7b</i> on melanogenesis may provide useful information for the future research on human melanoma-related diseases.