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 J Robbins, Yashi Ahmed, Ethan Lee

Research output: Contribution to journalArticle

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 1 2019

Fingerprint

Uridine Diphosphate
Wnt Signaling Pathway
Glycosylation
Growth
Congenital Disorders of Glycosylation
Xenopus laevis
Zebrafish
Drosophila
Embryonic Development
Phosphotransferases
Maintenance

Keywords

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

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

Cite this

Neitzel, L. R., Spencer, Z. T., Nayak, A., Cselenyi, C. S., Benchabane, H., Youngblood, C. A. Q., ... 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

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 journalArticle

Neitzel, LR, Spencer, ZT, Nayak, A, Cselenyi, CS, Benchabane, H, Youngblood, CAQ, Zouaoui, A, Ng, V, Stephens, L, Hann, T, Patton, JG, Robbins, DJ, Ahmed, Y & Lee, E 2019, 'Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway', Mechanisms of Development, vol. 156, pp. 20-31. https://doi.org/10.1016/j.mod.2019.03.002
Neitzel LR, Spencer ZT, Nayak A, Cselenyi CS, Benchabane H, Youngblood CAQ et al. Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway. Mechanisms of Development. 2019 Apr 1;156:20-31. https://doi.org/10.1016/j.mod.2019.03.002
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. / Developmental regulation of Wnt signaling by Nagk and the UDP-GlcNAc salvage pathway. In: Mechanisms of Development. 2019 ; Vol. 156. pp. 20-31.
@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 Robbins, {David J} and Yashi Ahmed and Ethan Lee",
year = "2019",
month = "4",
day = "1",
doi = "10.1016/j.mod.2019.03.002",
language = "English (US)",
volume = "156",
pages = "20--31",
journal = "Mechanisms of Development",
issn = "0925-4773",
publisher = "Elsevier Ireland Ltd",

}

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

C2 - 30904594

AN - SCOPUS:85063897461

VL - 156

SP - 20

EP - 31

JO - Mechanisms of Development

JF - Mechanisms of Development

SN - 0925-4773

ER -