O-GlcNAcylation Dampens Dpp/BMP Signaling to Ensure Proper Drosophila Embryonic Development

Moulton, Matthew J.; Humphreys, Gregory B.; Kim, Alexander; Letsou, Anthea

doi:10.1016/j.devcel.2020.04.001

Cited by 16 publications

(20 citation statements)

References 102 publications

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“…The UDP-N-acetylglucosamine pyrophosphorylase Mummy, a key enzyme catalyzes the formation of UDP-GlcNAc, antagonizes the Dpp/BMP signaling 44 . Furthermore O-GlcNAcylation inhibits the Dpp/BMP type I receptor Sax 45 . Our results reveal that at transcriptional level, low O-GlcNAcylation via polycomb repression inhibits the expression of the Dpp/BMP antagonist sog .…”

Section: Discussionmentioning

confidence: 99%

A mutant bacterial O-GlcNAcase visualizes a progressive decline of protein O-GlcNAcylation in early Drosophila embryos critical for neurodevelopment

Zhang

Wang

et al. 2022

Preprint

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Protein O-GlcNAcylation, a monosaccharide posttranslational modification maintained by two evolutionarily conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is a major nutrient sensor integrating key metabolic pathways. While mutations in OGT have recently been associated with neurodevelopmental disorders, the dynamics and function of protein O-GlcNAcylation during early embryogenesis remain elusive. Here we develop a new fluorescent probe to visualize O-GlcNAcylation levels in live Drosophila early embryos. Our study shows that protein O-GlcNAcylation declines as the embryos develop to the mid-blastula transition when the facultative heterochromatin makes its first appearance. Lowering O-GlcNAcylation levels by exogenous OGA activity promotes the polycomb group O-GlcNAc protein Polyhomeotic (Ph) to form nuclear foci and K27 trimethylation of histone H3. This enhanced facultative heterochromatin formation fine-tunes the expression of several neurodevelopmental genes including short of gastrulation (sog). We provide evidence that perturbation of O-GlcNAcylation during early embryogenesis affects learning ability in adulthood, highlighting the importance of O-GlcNAcylation homeostasis for the development of the nervous system.

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Section: Discussionmentioning

confidence: 99%

A mutant bacterial O-GlcNAcase visualizes a progressive decline of protein O-GlcNAcylation in early Drosophila embryos critical for neurodevelopment

Zhang

Wang

et al. 2022

Preprint

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“…Glycosylation of ECM proteins has been linked to morphogenetic programs in other model organisms ( Holt and Dickson, 2005 ; Humphreys et al 2013 ; Poulain and Yost 2015 ; Basak et al 2016 Moulton et al 2020 ). While post-translational GlcNAc modifications to proteins are linked to regulating morphogenesis, the mechanisms by which they regulate cell movement and migration are not well understood.…”

Section: Discussionmentioning

confidence: 99%

A genetic screen for temperature-sensitive morphogenesis-defective Caenorhabditis elegans mutants

Jud

Lowry

Padilla

et al. 2021

G3 Genes|Genomes|Genetics

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Morphogenesis involves coordinated cell migrations and cell shape changes that generate tissues and organs, and organize the body plan. Cell adhesion and the cytoskeleton are important for executing morphogenesis, but their regulation remains poorly understood. As genes required for embryonic morphogenesis may have earlier roles in development, temperature-sensitive embryonic-lethal mutations are useful tools for investigating this process. From a collection of ∼200 such Caenorhabditis elegans mutants, we have identified 17 that have highly penetrant embryonic morphogenesis defects after upshifts from the permissive to the restrictive temperature, just prior to the cell shape changes that mediate elongation of the ovoid embryo into a vermiform larva. Using whole genome sequencing, we identified the causal mutations in seven affected genes. These include three genes that have roles in producing the extracellular matrix, which is known to affect the morphogenesis of epithelial tissues in multicellular organisms: the rib-1 and rib-2 genes encode glycosyltransferases, and the emb-9 gene encodes a collagen subunit. We also used live imaging to characterize epidermal cell shape dynamics in one mutant, or1219ts, and observed cell elongation defects during dorsal intercalation and ventral enclosure that may be responsible for the body elongation defects. These results indicate that our screen has identified factors that influence morphogenesis and provides a platform for advancing our understanding of this fundamental biological process.

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“…receptor Sax by O-GlcNAcylation [44], and the stability of Wnt signalling nodes CK2 and β-catenin are negatively and positively regulated by O-GlcNAc, respectively [45,46]. O-GlcNAcylation of Synapsin I, which is also identified as a candidate conveyer J o u r n a l P r e -p r o o f in this study (Supplementary Table 1), regulates presynaptic vesicle dynamics and the size of the reserve pool of synaptic vesicles [14].…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Bioinformatic prediction of putative conveyers of O-GlcNAc transferase intellectual disability

Mitchell

Czajewski²,

Aalten³

2022

Journal of Biological Chemistry

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O-GlcNAcylation Dampens Dpp/BMP Signaling to Ensure Proper Drosophila Embryonic Development

Cited by 16 publications

References 102 publications

A mutant bacterial O-GlcNAcase visualizes a progressive decline of protein O-GlcNAcylation in early Drosophila embryos critical for neurodevelopment

A mutant bacterial O-GlcNAcase visualizes a progressive decline of protein O-GlcNAcylation in early Drosophila embryos critical for neurodevelopment

A genetic screen for temperature-sensitive morphogenesis-defective Caenorhabditis elegans mutants

Bioinformatic prediction of putative conveyers of O-GlcNAc transferase intellectual disability

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