Core fucosylation is required for midline patterning during zebrafish development

Seth, Anandita; Machingo, Quentin J.; Fritz, Andreas; Shur, Barry D.

doi:10.1002/dvdy.22475

Cited by 13 publications

(12 citation statements)

References 86 publications

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“…Yan et al have demonstrated O -fucosylation of Notch receptors to control blood lineage commitment [26] . In another study by Seth et al, they have demonstrated that core O -fucosylation of apolipoprotein B is required for proper midline patterning during zebrafish development by modulating the sonic hedgehog signaling [27] . These studies display the significance of glycosylation in mediating the embryonic development process.…”

Section: Stem Cells and Glycosylationmentioning

confidence: 99%

Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis

et al. 2018

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Aberrant glycosylation plays a critical role in tumor aggressiveness, progression, and metastasis. Emerging evidence associates cancer initiation and metastasis to the enrichment of cancer stem cells (CSCs). Several universal markers have been identified for CSCs characterization; however, a specific marker has not yet been identified for different cancer types. Specific glycosylation variation plays a major role in the progression and metastasis of different cancers. Interestingly, many of the CSC markers are glycoproteins and undergo differential glycosylation. Given the importance of CSCs and altered glycosylation in tumorigenesis, the present review will discuss current knowledge of altered glycosylation of CSCs and its application in cancer research.

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Section: Stem Cells and Glycosylationmentioning

confidence: 99%

Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis

et al. 2018

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“…The glycosylation of macromolecules, including proteins and lipids, is critically involved in the regulation of numerous biochemical and physiological activities in eukaryotic cells 1 . It is known that glycosylation plays essential roles to ensure normal cell differentiation and embryogenesis 2 3 4 , but its function in human pluripotent stem cells (hPSCs) remains largely unclear. A recent report demonstrated that O -linked glycosylation influences cellular pluripotency by acting on core components of the pluripotency signaling network in mouse embryonic stem cells (mESCs) 5 , revealing a direct link between protein glycosylation and pluripotency regulation that is highly likely to exist in human cells.…”

mentioning

confidence: 99%

Glycosyltransferase ST6GAL1 contributes to the regulation of pluripotency in human pluripotent stem cells

Wang

Stein

Lynch

et al. 2015

Sci Rep

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Many studies have suggested the significance of glycosyltransferase-mediated macromolecule glycosylation in the regulation of pluripotent states in human pluripotent stem cells (hPSCs). Here, we observed that the sialyltransferase ST6GAL1 was preferentially expressed in undifferentiated hPSCs compared to non-pluripotent cells. A lectin which preferentially recognizes α-2,6 sialylated galactosides showed strong binding reactivity with undifferentiated hPSCs and their glycoproteins, and did so to a much lesser extent with differentiated cells. In addition, downregulation of ST6GAL1 in undifferentiated hPSCs led to a decrease in POU5F1 (also known as OCT4) protein and significantly altered the expression of many genes that orchestrate cell morphogenesis during differentiation. The induction of cellular pluripotency in somatic cells was substantially impeded by the shRNA-mediated suppression of ST6GAL1, partially through interference with the expression of endogenous POU5F1 and SOX2. Targeting ST6GAL1 activity with a sialyltransferase inhibitor during cell reprogramming resulted in a dose-dependent reduction in the generation of human induced pluripotent stem cells (hiPSCs). Collectively, our data indicate that ST6GAL1 plays an important role in the regulation of pluripotency and differentiation in hPSCs, and the pluripotent state in human cells can be modulated using pharmacological tools to target sialyltransferase activity.

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“…A role for core fucosylation during midline patterning and retinal and motor neuron development has also been demonstrated. Knockdown of fut8 , as well as one of the principal fut8 substrates, apolipoprotein B (ApoB), phenocopies defects noted in mutants of Sonic Hedgehog (Shh) signaling ( smu, syu, yot ) [72]. As had previously been demonstrated in Drosophila, these results indicate that altered core fucosylation of ApoB impacts Shh signaling, possibly by affecting its transport.…”

Section: Role Of Glycans In Zebrafish Developmentmentioning

confidence: 85%

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

Flanagan-Steet

Steet

2012

Glycoconj J

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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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Core fucosylation is required for midline patterning during zebrafish development

Cited by 13 publications

References 86 publications

Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis

Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis

Glycosyltransferase ST6GAL1 contributes to the regulation of pluripotency in human pluripotent stem cells

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

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