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Mannose controls mesoderm specification and symmetry breaking in mouse gastruloids.

Accepted version
Peer-reviewed

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Authors

Dingare, Chaitanya 
Cao, Dominica 
Yang, Jenny Jingni 
Sozen, Berna 
Steventon, Benjamin  ORCID logo  https://orcid.org/0000-0001-7838-839X

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.

Description

Keywords

FGF, Wnt, gastrulation, gastruloids, glycosylation, metabolomics, self-organisation, Animals, Mesoderm, Mice, Mannose, Glycosylation, Deoxyglucose, Wnt Signaling Pathway, Gastrula, Body Patterning, Gene Expression Regulation, Developmental, Cell Differentiation, Mouse Embryonic Stem Cells, Frizzled Receptors

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (109408/Z/15/Z)
Wellcome Trust (225360/Z/22/Z)
MRC (MR/V009192/1)