ZFIN ID: ZDB-PUB-060508-14
A β1,4-galactosyltransferase is required for Bmp2-dependent patterning of the dorsoventral axis during zebrafish embryogenesis
Machingo, Q.J., Fritz, A., and Shur, B.D.
Date: 2006
Source: Development (Cambridge, England)   133(11): 2233-2241 (Journal)
Registered Authors: Fritz, Andreas
Keywords: Galactosyltransferase, Bmp, Zebrafish, Embryonic axis
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Body Patterning*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins/genetics
  • Bone Morphogenetic Proteins/metabolism*
  • Cloning, Molecular
  • Embryo, Nonmammalian/embryology*
  • Embryo, Nonmammalian/enzymology*
  • Embryo, Nonmammalian/metabolism
  • Galactosyltransferases/chemistry
  • Galactosyltransferases/deficiency
  • Galactosyltransferases/genetics
  • Galactosyltransferases/metabolism*
  • Gene Expression Regulation, Developmental
  • Glycoproteins/metabolism
  • Glycosylation
  • Humans
  • Intercellular Signaling Peptides and Proteins/metabolism
  • Molecular Sequence Data
  • Molecular Weight
  • Phenotype
  • Phylogeny
  • Protein Binding
  • Proteoglycans/metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Smad Proteins
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed: 16672343 Full text @ Development
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ABSTRACT
Complex carbohydrates are highly polymorphic macromolecules that are involved in diverse biological processes; however, a detailed understanding of their function remains obscure. To better define the roles of complex carbohydrates during vertebrate embryogenesis, we have initiated an analysis of glycosyltransferase function using the zebrafish system. In this study, we report the characterization of a zebrafish beta1,4-galactosyltransferase (GalT), which has substantial homology with mammalian beta4GalT5 and is expressed zygotically throughout the zebrafish embryo. Downregulating the expression of beta4GalT5 by injection of specific morpholino oligonucleotides results in dorsalized zebrafish embryos, suggesting a role of beta4GalT5 in Bmp2-mediated specification of the dorsoventral axis. Consistent with this, morpholino-injected embryos have ventrally expanded chordin expression and reduced activation of the Bmp-dependent transcription factors Smad1/5/8. Because other growth factors, such as Egf and Fgf, require binding to extracellular proteoglycans for delivery and/or binding to their cognate receptors, we examined whether proteoglycans isolated from control and morpholino-injected embryos show differential binding affinities for Bmp2. In this regard, proteoglycans isolated from beta4GalT5 morphant embryos are underglycosylated and are unable to bind recombinant Bmp2 as efficiently as proteoglycans from control-injected embryos, whereas the binding of Bmp7 is relatively unaffected. These results suggest that beta4GalT5 is a previously unidentified zebrafish galactosyltransferase that is essential for proper patterning of the dorsoventral axis by regulating Bmp2 signaling. Furthermore, this work demonstrates that a relatively simple carbohydrate modification to endogenous proteoglycans can modulate the specificity of cytokine signaling.
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