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Mannose controls mesoderm specification and symmetry breaking in mouse gastruloids.
- Source :
-
Developmental cell [Dev Cell] 2024 Jun 17; Vol. 59 (12), pp. 1523-1537.e6. Date of Electronic Publication: 2024 Apr 17. - Publication Year :
- 2024
-
Abstract
- Patterning and growth are fundamental features of embryonic development that must be tightly coordinated. To understand how metabolism impacts early mesoderm development, we used mouse embryonic stem-cell-derived gastruloids, that co-expressed glucose transporters with the mesodermal marker T/Bra. We found that the glucose mimic, 2-deoxy-D-glucose (2-DG), blocked T/Bra expression and abolished axial elongation in gastruloids. However, glucose removal did not phenocopy 2-DG treatment despite a decline in glycolytic intermediates. As 2-DG can also act as a competitive inhibitor of mannose in protein glycosylation, we added mannose together with 2-DG and found that it could rescue the mesoderm specification both in vivo and in vitro. We further showed that blocking production and intracellular recycling of mannose abrogated mesoderm specification. Proteomics analysis demonstrated that mannose reversed glycosylation of the Wnt pathway regulator, secreted frizzled receptor Frzb. Our study showed how mannose controls mesoderm specification in mouse gastruloids.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Glycosylation
Deoxyglucose metabolism
Deoxyglucose pharmacology
Wnt Signaling Pathway drug effects
Gastrula metabolism
Body Patterning drug effects
Body Patterning genetics
Gene Expression Regulation, Developmental drug effects
Cell Differentiation drug effects
Mouse Embryonic Stem Cells metabolism
Mouse Embryonic Stem Cells cytology
Mouse Embryonic Stem Cells drug effects
Frizzled Receptors metabolism
Frizzled Receptors genetics
Mesoderm metabolism
Mannose metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 59
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 38636516
- Full Text :
- https://doi.org/10.1016/j.devcel.2024.03.031