PUBLICATION
A transcriptional and post-transcriptional dysregulation of Dishevelled 1 and 2 underlies the Wnt signaling impairment in type I Gaucher disease experimental models
- Authors
- Costa, R., Bellesso, S., Lualdi, S., Manzoli, R., Pistorio, V., Filocamo, M., Moro, E.
- ID
- ZDB-PUB-200528-18
- Date
- 2020
- Source
- Human molecular genetics 29: 285 (Journal)
- Registered Authors
- Bellesso, Stefania, Costa, Roberto, Manzoli, Rosa, Moro, Enrico
- Keywords
- gaucher disease signal transduction transcription, genetic fibroblasts glucosylceramidase transducers
- MeSH Terms
-
- 3' Untranslated Regions
- Adaptor Proteins, Vesicular Transport/genetics
- Adaptor Proteins, Vesicular Transport/metabolism
- Animals
- Animals, Genetically Modified
- Cell Line
- Disease Models, Animal
- Dishevelled Proteins/genetics
- Dishevelled Proteins/metabolism*
- Gaucher Disease/enzymology
- Gaucher Disease/genetics
- Gaucher Disease/metabolism*
- Glucosylceramidase/genetics
- Glucosylceramidase/metabolism*
- Humans
- Intracellular Signaling Peptides and Proteins/genetics
- Intracellular Signaling Peptides and Proteins/metabolism
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Osteoblasts/enzymology
- Osteoblasts/metabolism
- Osteoblasts/pathology
- Transcription, Genetic
- Wnt Signaling Pathway/genetics*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 31816052 Full text @ Hum. Mol. Genet.
Citation
Costa, R., Bellesso, S., Lualdi, S., Manzoli, R., Pistorio, V., Filocamo, M., Moro, E. (2020) A transcriptional and post-transcriptional dysregulation of Dishevelled 1 and 2 underlies the Wnt signaling impairment in type I Gaucher disease experimental models. Human molecular genetics. 29:285.
Abstract
Bone differentiation defects have been recently tied to Wnt signaling alterations occurring in vitro and in vivo Gaucher disease (GD) models. In this work, we provide evidence that the Wnt signaling multi-domain intracellular transducers Dishevelled 1 and 2 (DVL1 and DVL2) may be potential upstream targets of impaired beta glucosidase (GBA1) activity by showing their misexpression in different type 1 GD in vitro models. We also show that in Gba mutant fish a miR-221 upregulation is associated with reduced dvl2 expression levels and that in type I Gaucher patients single-nucleotide variants in the DVL2 3′ untranslated region are related to variable canonical Wnt pathway activity. Thus, we strengthen the recently outlined relation between bone differentiation defects and Wnt/β-catenin dysregulation in type I GD and further propose novel mechanistic insights of the Wnt pathway impairment caused by glucocerebrosidase loss of function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping