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 language | English (US) |
|---|---|
| Pages (from-to) | 20-31 |
| Number of pages | 12 |
| Journal | Mechanisms of Development |
| Volume | 156 |
| DOIs | |
| State | Published - Apr 1 2019 |
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Keywords
- Development
- Nagk
- UDP-GlcNAc salvage pathway
- Wnt signaling
ASJC Scopus subject areas
- Embryology
- Developmental Biology
Cite this
Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway. / Neitzel, Leif R.; Spencer, Zachary T.; Nayak, Anmada; Cselenyi, Christopher S.; Benchabane, Hassina; Youngblood, Chey Anne Q.; Zouaoui, Alya; Ng, Victoria; Stephens, Leah; Hann, Trevor; Patton, James G.; Robbins, David J; Ahmed, Yashi; Lee, Ethan.
In: Mechanisms of Development, Vol. 156, 01.04.2019, p. 20-31.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway
AU - Neitzel, Leif R.
AU - Spencer, Zachary T.
AU - Nayak, Anmada
AU - Cselenyi, Christopher S.
AU - Benchabane, Hassina
AU - Youngblood, Chey Anne Q.
AU - Zouaoui, Alya
AU - Ng, Victoria
AU - Stephens, Leah
AU - Hann, Trevor
AU - Patton, James G.
AU - Robbins, David J
AU - Ahmed, Yashi
AU - Lee, Ethan
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
KW - Development
KW - Nagk
KW - UDP-GlcNAc salvage pathway
KW - Wnt signaling
UR - http://www.scopus.com/inward/record.url?scp=85063897461&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063897461&partnerID=8YFLogxK
U2 - 10.1016/j.mod.2019.03.002
DO - 10.1016/j.mod.2019.03.002
M3 - Article
VL - 156
SP - 20
EP - 31
JO - Mechanisms of Development
JF - Mechanisms of Development
SN - 0925-4773
ER -