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XB-ART-55795
Mech Dev January 1, 2019; 156 20-31.

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

Neitzel LR , Spencer ZT , Nayak A , Cselenyi CS , Benchabane H , Youngblood CQ , Zouaoui A , Ng V , Stephens L , Hann T , Patton JG , Robbins D , Ahmed Y , Lee E .


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: 30904594
PMC ID: PMC6574174
Article link: Mech Dev
Grant support: [+]
Genes referenced: chrd.1 dpagt1 dusp6 dvl2 fzd5 hes1 lrp6 nagk nodal nodal3.1 nodal3.2 notch1 odc1 pgm3 psmd6 ptch1 shh tbxt uap1 wnt8a
Morpholinos: dpagt1 MO1 nagk MO1 pgm3 MO1 uap1 MO1


Article Images: [+] show captions


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