UDP-glucose dehydrogenase (UGDH) supplies the cell with UDP-glucuronic acid, a precursor of glycosaminoglycan and proteoglycan synthesis. In this study, we report the cloning and the characterization of the UGDH from the amphibian Xenopus laevis that is one of the model organisms for developmental biology. We found that X. laevis UGDH (xUGDH) maintained a very high degree of similarity with other known UGDH sequences both at the genomic and the protein levels. Also its kinetic parameters are similar to those of UGDH from other species. During X. laevis development, UDGH is always expressed, but clearly increases its mRNA levels at the tailbud stage (i.e., 30 hours post fertilization). This result fits well with our previous observation that hyaluronan, a glycosaminoglycan that is synthesized using UDP-glucuronic acid and UDP-N-acetylglucosamine, is abundantly detected at this developmental stage. The expression of UGDH was found to be related to hyaluronan (HA) synthesis. In human smooth muscle cells the overexpression of xUGDH or endogenous abrogation of UGDH modulated HA synthesis specifically. Our findings were confirmed by in vivo experiments where the silencing of xUGDH in X. laevis embryos decreased glycosaminoglycan synthesis causing severe embryonic malformations due to a defective gastrulation process.