title: GNE is involved in the early development of skeletal and cardiac muscle.
abstract: UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamime kinase (GNE) is a bifunctional enzyme which catalyzes the two key sequential steps in the biosynthetic pathway of sialic acid, the most abundant terminal monosaccharide on glycoconjugates of eukaryotic cells. GNE knock out (GNE KO) mice are embryonically lethal at day E8.5. Although the role of GNE in the sialic pathway has been well established as well as the importance of sialylation in many diverse biological pathways, less is known about the involvement of GNE in muscle development. To address this issue we have studied the role of GNE during in vitro embryogenesis by comparing the developmental profile in culture of embryonic stem cells (ES) from wild type and from GNE KO E3.5 mice embryos, during 45 days. Neuronal cells appeared rarely in GNE KO ES cultures and did not reach an advanced differentiated stage. Although primary cardiac cells appeared at the same time in both normal and GNE KO ES cultures, GNE KO cardiac cells degraded very soon and their beating capacity decayed rapidly. Furthermore very rare skeletal muscle committed cells were detected in the GNE KO ES cultures at any stage of differentiation, as assessed by analysis of the expression of either Pax7, MyoD and MyHC markers. Beyond the supporting evidence that GNE plays an important role in neuronal cell and brain development, these results show that GNE is strongly involved in cardiac tissue and skeletal muscle early survival and organization. These findings could open new avenues in the understanding of muscle function mechanisms in health and in disease.
authors: Goldyne Savad Institute for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors: Irit
authors: I
authors: Milman Krentsis
authors: Ilan
authors: I
authors: Sela
authors: Rachel
authors: R
authors: Eiges
authors: Véronique
authors: V
authors: Blanchard
authors: Markus
authors: M
authors: Berger
authors: Michal
authors: M
authors: Becker Cohen
authors: Stella
authors: S
authors: Mitrani-Rosenbaum
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000172:deficiency / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000254:growth & development*; D009206:Myocardium / Q000201:enzymology*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D009097:Multienzyme Complexes; C482901:UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase; D019158:N-Acetylneuraminic Acid