Abstract
Syndecans belong to a four-member family of cell surface heparan sulfate proteoglycans (HSPGs) abundantly present in various tissues. They are primarily recognized as extracellular matrix (ECM) receptors able to bind various ECM components and form gradients of morphogens and growth factors. Syndecans are composed of core protein with distinctive cytoplasmic, transmembrane, and extracellular domains to which several HS glycosaminoglycan (GAG) chains are covalently attached. In development of composite organs, such as teeth, expression patterns of syndecans display temporo-spatial shifts between epithelial and mesenchymal tissue compartments. Along with diverse functional properties of syndecans and generally large number of their interactors due to HS GAG chain content, this suggests possible involvement of syndecans in modulation of epithelial-to-mesenchymal crosstalk. Functional versatility of syndecans greatly depends upon the biochemical properties of attached HS GAG chains. These are specifically determined during the HS biosynthesis by the combinatorial action of glycosyl-transferases (Exts/EXTs) and bi-functional sulfotransferases (Ndsts/NDSTs), as well as by post-biosynthetic enzymatic cleavage of HS by the only active endoglucuronidase in mammals, heparanase 1 (Hpse1/HPSE1). Matching the essential requirement for HS during organogenesis, null-mutant animals for genes encoding these enzymes display severe developmental anomalies of mineralized tissues (including teeth) with embryonic or perinatal lethality. In this study, we analyzed expression of syndecan HSPGs (syndecans 1, 2, and 4), enzymes involved in HS biosynthesis (EXT1, NDST1, NDST2) and HS cleavage (HPSE1) in human tooth germs during the early stages of odontogenesis. All of the investigated factors displayed temporo-spatial differences in expression patterns, and some of them showed distinctive asymmetries of expression domains. Our findings suggest that these factors might be differentially involved in cellular processes which take place during the early odontogenic sequence in humans.
Highlights
Syndecans belong to a small family of cell surface heparan sulfate proteoglycans (HSPGs) and are one of the most abundant cell surface receptors (Gotte, 2003; Stepp et al, 2015)
We analyzed expression domains and patterns of syndecans (Sdc1, Sdc2, and Sdc4) and enzymes involved in biosynthesis (EXT1, NDST1, and NDST2) and cleavage (HPSE1) of HS GAGs in human incisor tooth germs during the late bud (7/8 gestational weeks), cap (11/12 gestational weeks), and early bell stage (14 gestational weeks) of development (Figure 1)
In contrast to Sdc2, Sdc4 was expressed in parts of dental follicle adjacent to cervical loops, and expression of both Sdc and Sdc4 was visible throughout the inner enamel epithelium and stratum intermedium in the early bell stage
Summary
Syndecans belong to a small family of cell surface heparan sulfate proteoglycans (HSPGs) and are one of the most abundant cell surface receptors (Gotte, 2003; Stepp et al, 2015). But are primarily recognized as ECM receptors and growth factor co-receptors due to their ability to bind various ECM components and growth factors via their HS GAG side chains (Bernfield et al, 1992; Roper et al, 2012; Teng et al, 2012). During the early stages of odontognesis, expression of Sdc shifts from epithelial to mesenchymal parts of tooth germ on a stagespecific basis. This is indicative of epithelial-to-mesenchymal crosstalk, through which the exchange of inductive odontogenic potential between the tooth germ tissue compartments occurs. The importance of epithelial-to-mesenchymal crosstalk for normal progression of tooth development has been demonstrated by numerous tissue recombination experiments, whereas its early disruption causes arrest of odontogenesis as observed in null-mutant animals for genes regulating jaw patterning and tooth number (Sharpe, 2001; Miletich and Sharpe, 2003; Chen et al, 2009; Ohazama et al, 2009; Kero and Saraga-Babic, 2016)
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