Intermuscular bones (IBs) are small spicule-like bones existing in the muscle fillet of fish and ossified from tendons, which only occur in lower teleosts. Most of the aquaculture fish species in the world, especially cyprinid fishes, contain a certain amount of IBs, which consequently affects the market value and processing industry of these species. Therefore, understanding the molecular regulation mechanism and conducting the genetic selection of IBs are worthwhile and meaningful for the world aquaculture industry, especially for carp species. Since 1967, more and more studies began to focus on the types, morphology and number of IBs among different fish species. With the evolution of fish, the IBs morphology evolved from simple to complex and then degenerate simple again. The two different types of ossification pattern have been observed during IBs’ development, including ossification from posterior to the anterior regions, and from anterior to the posterior regions. Recently, with the development of high-throughput sequencing and molecular technology, a quite number of studies have been conducted and tried to uncover the molecular mechanisms of IBs development. The regulation functions of some genes, such as scxa
, had been revealed. Among these genes, the scxa
mutations based on Crispr/Cas9 system showed distinct reduction of mineralized IBs in zebrafish, osterix
mutations in common carp had short length of IBs. These genes could be used as candidate genes to breed less or short IBs strains in other economic fish species with IBs. The omics data of IBs, including miRNA, mRNA, proteomics and genomics, have been established in several fish species, such as blunt snout bream, common carp, tambaqui, which would be useful to unveil the molecular regulation mechanisms of IBs development. As to the genetic selection of IBs, several technologies, such as selective breeding, hybridization, polyploid breeding, gynogenesis and gene editing, had been used to breed strains with less IBs number. The selective breeding studies had reported the moderate heritability values of IBs number in blunt snout bream and mirror carp, which indicate that it should be feasible to decrease the number of IBs through selective breeding. Some related SNPs and QTL with IBs number were also identified in these two species. The individuals totally losing IBs were identified in the grass carp gynogenetic population in China and in one tambaqui culture population in Brazil. These identified individuals offers the fantastic materials for understanding the genetic origin of this phenotype as well as founders to breed offspring without IBs. In the future, with the development of single cell transcriptomics and spatially resolved transcriptomics analysis, the molecular mechanism for tendon-derived stem cells differentiating into osteoblast in species with IBs could be clarified. Then the key genes could be screened out and their functions in IBs development can be clarified. Moreover, Genome wide association studies (GWAS) based on sequencing could be used to identify the genes/SNPs associated with IBs number and whole genome selection approach could be considered in some important species. In this review, we summarized all the related reports focusing on fish IBs’ developmental molecular mechanism and genetic breeding, and the future directions are also discussed, which could dedicate basic data for less-IB or no-IB strains breeding program.