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First published online 3 May 2006
doi: 10.1242/dev.02378

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A ß1,4-galactosyltransferase is required for Bmp2-dependent patterning of the dorsoventral axis during zebrafish embryogenesis

¹ Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
² Department of Biology, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.

^* Author for correspondence (e-mail: barry{at}cellbio.emory.edu)

Accepted 28 March 2006

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 ß1,4-galactosyltransferase (GalT), which has substantial homology with mammalian ß4GalT5 and is expressed zygotically throughout the zebrafish embryo. Downregulating the expression of ß4GalT5 by injection of specific morpholino oligonucleotides results in dorsalized zebrafish embryos, suggesting a role of ß4GalT5 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 ß4GalT5 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 ß4GalT5 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.

Key words: Galactosyltransferase, Bmp, Zebrafish, Embryonic axis

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