Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway

Leif R. Neitzel, Zachary T. Spencer, Anmada Nayak, Christopher S. Cselenyi, Hassina Benchabane, Chey Anne Q. Youngblood, Alya Zouaoui, Victoria Ng, Leah Stephens, Trevor Hann, James G. Patton, David Robbins, Yashi Ahmed, Ethan Lee

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalMechanisms of Development
Volume156
DOIs
StatePublished - Apr 2019

Keywords

  • Development
  • Nagk
  • UDP-GlcNAc salvage pathway
  • Wnt signaling

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

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    Neitzel, L. R., Spencer, Z. T., Nayak, A., Cselenyi, C. S., Benchabane, H., Youngblood, C. A. 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. Mechanisms of Development, 156, 20-31. https://doi.org/10.1016/j.mod.2019.03.002