Two families of Xenopus tropicalis skeletal genes display well‐conserved expression patterns with mammals in spite of their highly divergent regulatory regions

Abstract

The origin of bone and cartilage, and their subsequent diversification in specific vertebrate lineages, is intimately linked to the precise transcriptional control of genes involved in matrix mineralization. It is not yet clear, however, to which extent the osteoblasts, osteocytes, and chondrocytes of each of the major vertebrate groups express similar sets of genes. In this study we have focused on the evolution of two independent families of genes that code for extracellular matrix components of the skeleton and that include secreted protein, acidic, cysteine-rich (SPARC), bone sialoprotein (BSP) and dentin matrix protein 1 (DMP1) paralogues, and the osteocalcin (OC) and matrix gla protein (MGP) paralogues. Analyzing developing Xenopus tropicalis skeletal elements, we show that the expression patterns of these genes are well conserved with mammals. The fact that only a few osteoblasts express DMP1, while only some osteocytes express SPARC and BSP, reveals a significant degree of molecular heterogeneity for these two populations of X. tropicalis cells, similarly to what has been described in mouse. Although the cis-regulatory modules (CRM) of the mammalian OC, DMP1, and BSP orthologs have been functionally characterized, we found no evidence of sequence similarity between these regions and the X. tropicalis genome. Furthermore, these regulatory elements evolve rapidly, as they are only poorly conserved between human and rodents. Therefore, the SPARC/DMP1/BSP and the OC/MGP families provide a good paradigm to study how transcriptional output can be maintained in skeletal cells despite extensive sequence divergence of CRM.

Evolution of dental tissue mineralization: an analysis of the jawed vertebrate SPARC and SPARC-L families

“…In Xenopus tropicalis , SPARC expression has previously been described during embryogenesis and osteogenesis, but not during odontogenesis [35, 58]. To evaluate whether the SPARC-L1 and SPARC-L2 loss was accompanied by compensatory mechanisms that might have involved changes in the expression domain of other related genes, we examined SPARC expression in developing teeth of Xenopus tropicalis.…”

Loss of bone sialoprotein leads to impaired endochondral bone development and mineralization

“…These proteins also contain integrinbinding RGD (Arginine-Glycine-Aspartate) sequences and highly acidic regions composed of (depending on the protein) poly-glutamate or poly-aspartate sequences. In BSP, the poly-glutamate sequences, which are highly conserved [16,17], are critical for hydroxyapatite (HA) nucleation activity based on in vitro studies [18]. The RGD sequence of BSP mediates cell attachment [19,20] but also has been demonstrated to promote osteoblastic cell differentiation and mineralization in vitro through cellular signaling pathways involving focal adhesion kinase and extracellular signal-regulated kinases [21].…”

A dynamic history of gene duplications and losses characterizes the evolution of the SPARC family in eumetazoans

“…Second, the SPARC family predates the emergence of vertebrates [13][14][15][16][17]. Third, among osteichthyans (bony fishes and tetrapods), most species exhibit two paralogues called SPARC and SPARCL1 that are expressed in skeletal cells [12,[18][19][20][21][22][23][24][25][26]. Finally, the SPARCL1 paralogue underwent a series of tandem duplications, thereby giving rise to the small calcium-binding phosphoproteins (SCPP) gene members [20,21].…”