Faculty Collaboration Database

Nutrient-driven O-linked N-acetylglucosamine (O-GlcNAc) cycling impacts neurodevelopmental timing and metabolism. J Biol Chem 2017 Apr 14;292(15):6076-6085

Date

03/02/2017

Pubmed ID

28246173

Pubmed Central ID

PMC5391740

DOI

10.1074/jbc.M116.774042

Scopus ID

2-s2.0-85018506290 (requires institutional sign-in at Scopus site)   56 Citations

Abstract

Nutrient-driven O-GlcNAcylation is strikingly abundant in the brain and has been linked to development and neurodegenerative disease. We selectively targeted the O-GlcNAcase (Oga) gene in the mouse brain to define the role of O-GlcNAc cycling in the central nervous system. Brain knockout animals exhibited dramatically increased brain O-GlcNAc levels and pleiotropic phenotypes, including early-onset obesity, growth defects, and metabolic dysregulation. Anatomical defects in the Oga knockout included delayed brain differentiation and neurogenesis as well as abnormal proliferation accompanying a developmental delay. The molecular basis for these defects included transcriptional changes accompanying differentiating embryonic stem cells. In Oga KO mouse ES cells, we observed pronounced changes in expression of pluripotency markers, including Sox2, Nanog, and Otx2. These findings link the O-GlcNAc modification to mammalian neurogenesis and highlight the role of this nutrient-sensing pathway in developmental plasticity and metabolic homeostasis.

Author List

Olivier-Van Stichelen S, Wang P, Comly M, Love DC, Hanover JA

Author

Stephanie Olivier-Van Stichelen PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylglucosamine
Animals
Brain
Mice
Mice, Knockout
Mouse Embryonic Stem Cells
N-Acetylglucosaminyltransferases
Nanog Homeobox Protein
Neurogenesis
Organ Specificity
Otx Transcription Factors
SOXB1 Transcription Factors