PUBLICATION
Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway
- Authors
- 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.
- ID
- ZDB-PUB-190326-4
- Date
- 2019
- Source
- Mechanisms of Development 156: 20-31 (Journal)
- Registered Authors
- Patton, James G.
- Keywords
- Development, Nagk, UDP-GlcNAc salvage pathway, Wnt signaling
- MeSH Terms
-
- Animals
- Body Patterning/genetics
- Drosophila/genetics
- Drosophila/growth & development
- Embryonic Development/genetics*
- Evolution, Molecular
- Gene Expression Regulation, Developmental
- Glycosylation
- Humans
- Phosphotransferases (Alcohol Group Acceptor)/genetics*
- Wnt Signaling Pathway/genetics*
- Xenopus laevis/genetics
- Xenopus laevis/growth & development*
- Zebrafish/genetics
- Zebrafish/growth & development
- PubMed
- 30904594 Full text @ Mech. Dev.
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. Mechanisms of Development. 156:20-31.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping