“Casting” light on the role of glycosylation during embryonic development: Insights from zebrafish

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.

The cellular and molecular progression of mitochondrial dysfunction induced by 2,4-dinitrophenol in developing zebrafish embryos

“…Each somite of the tail contains a small number of primary motor neurons that exit the neural tube; by 24 hpf they have yet to elaborate their full axonal arbor, but have begun to make synaptic contacts with the tail musculature (Flanagan-Steet and Steet, 2013; Meyers et al, 1986). We used the znp1/zn1 monoclonal antibody combination to label the motor neurons (Fig.…”

Integrative View of α2,3-Sialyltransferases (ST3Gal) Molecular and Functional Evolution in Deuterostomes: Significance of Lineage-Specific Losses

“…Up to now, adult tissue distribution of st3gal genes has been mainly studied in mouse and human tissues ( Gagneux and Varki 1999 ; Comelli et al 2006 ; Takashima 2008 ) whereas limited sialyltransferase expression studies were carried out in the zebrafish model ( Chang et al 2009 ; Harduin-Lepers 2010 ; Petit et al 2010 ; Vanbeselaere et al 2012 ; Flanagan-Steet and Steet 2013 ). The zebrafish st3gal gene expression profiles were analyzed in the light of evolution in adult tissues, using RT-PCR and in embryonic zebrafish tissues, using ISH.…”

Discovery Sulfoglycomics and Identification of the Characteristic Fragment Ions for High-Sensitivity Precise Mapping of Adult Zebrafish Brain–Specific Glycotopes

“…Zebrafish is an excellent model organism that is genetically friendly to allow for a whole range of developmental glycobiology studies (Flanagan-Steet and Steet 2013;de Abreu et al, 2020). With each target glycan manipulation, or changes in the expression of any one or several glycosyltransferases, we require not only efficient functional readout but also rapid mapping of anticipated glycomic changes at desirable spatiotemporal resolution, using as little sample material as possible without compromising the requisite structural details.…”