@article{e0c64fdffc8c48fd9dc18649fb3ffc44,
title = "Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway",
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.",
keywords = "Development, Nagk, UDP-GlcNAc salvage pathway, Wnt signaling",
author = "Neitzel, {Leif R.} and Spencer, {Zachary T.} and Anmada Nayak and Cselenyi, {Christopher S.} and Hassina Benchabane and Youngblood, {Chey Anne Q.} and Alya Zouaoui and Victoria Ng and Leah Stephens and Trevor Hann and Patton, {James G.} and David Robbins and Yashi Ahmed and Ethan Lee",
note = "Funding Information: We would like to thank Emilio Tahinci for Xenopus embryo injections, Emily Crispi for her assistance in preparing reagents and animal care, and Laura Lee for reading the manuscript. This work was funded by NIH grants R01CA105038, R01GM122222, R01121421, and the Norris Cotton Cancer Center to Y.A.; R35GM122516 and CTSA award (UL1TR000445) from the National Center for Advancing Translational Sciences to E.L.; R01CA219189 to D.J.R.; RO1EY024354 to J.G.P. E.L. and D.J.R. are co-founders of StemSynergy Therapeutics Inc. a company that seeks to develop inhibitors of major signaling pathways (including the Wnt pathway) for the treatment of cancer. Funding Information: We would like to thank Emilio Tahinci for Xenopus embryo injections, Emily Crispi for her assistance in preparing reagents and animal care, and Laura Lee for reading the manuscript. This work was funded by NIH grants R01CA105038 , R01GM122222 , R01121421 , and the Norris Cotton Cancer Center to Y.A.; R35GM122516 and CTSA award ( UL1TR000445 ) from the National Center for Advancing Translational Sciences to E.L.; R01CA219189 to D.J.R.; RO1EY024354 to J.G.P. Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",
year = "2019",
month = apr,
doi = "10.1016/j.mod.2019.03.002",
language = "English (US)",
volume = "156",
pages = "20--31",
journal = "Cells and Development",
issn = "2667-291X",
publisher = "Elsevier BV",
}