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Citation
Neitzel, L.R., Spencer, Z.T., Nayak, A., Cselenyi, C.S., Benchabane, H., Youngblood, C.Q., Zouaoui, A., Ng, V., Stephens, L., Hann, T., Patton, J.G., Robbins, D., Ahmed, Y., Lee, E. (2019). Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway.  Mech. Dev. 156(): 20--31.
FlyBase ID
FBrf0242164
Publication Type
Research paper
Abstract

In a screen for human kinases that regulate Xenopus laevis embryogenesis, we identified Nagk and other components of the UDP-GlcNAc glycosylation salvage pathway as regulators of anteroposterior patterning and Wnt signaling. We find that the salvage pathway does not affect other major embryonic signaling pathways (Fgf, TGFβ, Notch, or Shh), thereby demonstrating specificity for Wnt signaling. We show that the role of the salvage pathway in Wnt signaling is evolutionarily conserved in zebrafish and Drosophila. Finally, we show that GlcNAc is essential for the growth of intestinal enteroids, which are highly dependent on Wnt signaling for growth and maintenance. We propose that the Wnt pathway is sensitive to alterations in the glycosylation state of a cell and acts as a nutritional sensor in order to couple growth/proliferation with its metabolic status. We also propose that the clinical manifestations observed in congenital disorders of glycosylation (CDG) in humans may be due, in part, to their effects on Wnt signaling during development.

PubMed ID
PubMed Central ID
PMC6574174 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mech. Dev.
    Title
    Mechanisms of Development
    Publication Year
    1990-
    ISBN/ISSN
    0925-4773
    Data From Reference
    Genes (3)