Developmental regulation of oligosialylation in zebrafish.

Unité de Glycobiologie Structurale et Fonctionnelle, UMR CNRS 8576, Université des Sciences et Technologies de Lille 1, 59655, Villeneuve d'Ascq, France.
Glycoconjugate Journal (Impact Factor: 1.88). 09/2008; 26(3):247-61. DOI:10.1007/s10719-008-9161-5
Source: PubMed

ABSTRACT Zebrafish appears as a relevant model for the functional study of glycoconjugates along vertebrate's development. Indeed, as a prelude to such studies, we have previously identified a vast array of potentially stage-specific glycoconjugates, which structures are reminiscent of glycosylation pathways common to all vertebrates. In the present study, we have focused on the identification and regulation of major protein and lipids associated alpha2-8-linked oligosialic acids motifs in the early development of zebrafish. By a combination of partial hydrolysis, anion exchange HPLC-FD and mass spectrometry, we demonstrated that glycoproteins and glycolipids differed by the extent and the nature of their substituting oligosialylated sequences. Furthermore, relative quantifications showed that alpha2-8-linked sialylation was differentially regulated in both families of glycoconjugates along development. Accordingly, we established that alpha2,8-sialyltransferase mRNA levels was directly correlated with changes of alpha2,8-sialylation status of glycolipids, but independent of those observed on major glycoproteins that appear to originate from the mother.

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    ABSTRACT: Zebrafish (Danio rerio) remains a versatile model organism for the investigation of early development and organogenesis, and has emerged as a valuable platform for drug discovery and toxicity evaluation [1-6]. Harnessing the genetic power and experimental accessibility of this system, three decades of research have identified key genes and pathways that control the development of multiple organ systems and tissues, including the heart, kidney, and craniofacial cartilage, as well as the hematopoietic, vascular, and central and peripheral nervous systems [7-31]. In addition to their application in large mutagenic screens, zebrafish has been used to model a variety of diseases such as diabetes, polycystic kidney disease, muscular dystrophy and cancer [32-36]. As this work continues to intersect with cellular pathways and processes such as lipid metabolism, glycosylation and vesicle trafficking, investigators are often faced with the challenge of determining the degree to which these pathways are functionally conserved in zebrafish. While they share a high degree of genetic homology with mouse and human, the manner in which cellular pathways are regulated in zebrafish during early development, and the differences in the organ physiology, warrant consideration before functional studies can be effectively interpreted and compared with other vertebrate systems. This point is particularly relevant for glycosylation since an understanding of the glycan diversity and the mechanisms that control glycan biosynthesis during zebrafish embryogenesis (as in many organisms) is still developing.Nonetheless, a growing number of studies in zebrafish have begun to cast light on the functional roles of specific classes of glycans during organ and tissue development. While many of the initial efforts involved characterizing identified mutants in a number of glycosylation pathways, the use of reverse genetic approaches to directly model glycosylation-related disorders is now increasingly popular. In this review, the glycomics of zebrafish and the developmental expression of their glycans will be briefly summarized along with recent chemical biology approaches to visualize certain classes of glycans within developing embryos. Work regarding the role of protein-bound glycans and glycosaminoglycans (GAG) in zebrafish development and organogenesis will also be highlighted. Lastly, future opportunities and challenges in the expanding field of zebrafish glycobiology are discussed.
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