PUBLICATION
Leucine-Rich Repeat Kinase-2 Controls the Differentiation and Maturation of Oligodendrocytes in Mice and Zebrafish
- Authors
- Filippini, A., Cannone, E., Mazziotti, V., Carini, G., Mutti, V., Ravelli, C., Gennarelli, M., Schiavone, M., Russo, I.
- ID
- ZDB-PUB-240728-13
- Date
- 2024
- Source
- Biomolecules 14(7): (Journal)
- Registered Authors
- Schiavone, Marco
- Keywords
- LRRK2, Parkinson’s disease, oligodendrocytes, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Differentiation*/genetics
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2*/genetics
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2*/metabolism
- Mice
- Mice, Knockout
- Myelin Basic Protein/genetics
- Myelin Basic Protein/metabolism
- Oligodendroglia*/cytology
- Oligodendroglia*/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 39062584 Full text @ Biomolecules
Citation
Filippini, A., Cannone, E., Mazziotti, V., Carini, G., Mutti, V., Ravelli, C., Gennarelli, M., Schiavone, M., Russo, I. (2024) Leucine-Rich Repeat Kinase-2 Controls the Differentiation and Maturation of Oligodendrocytes in Mice and Zebrafish. Biomolecules. 14(7):.
Abstract
Leucine-rich repeat kinase-2 (LRRK2), a gene mutated in familial and sporadic Parkinson's disease (PD), controls multiple cellular processes important for GLIA physiology. Interestingly, emerging studies report that LRRK2 is highly expressed in oligodendrocyte precursor cells (OPCs) compared to the pathophysiology of other brain cells and oligodendrocytes (OLs) in PD. Altogether, these observations suggest crucial function(s) of LRRK2 in OPCs/Ols, which would be interesting to explore. In this study, we investigated the role of LRRK2 in OLs. We showed that LRRK2 knock-out (KO) OPC cultures displayed defects in the transition of OPCs into OLs, suggesting a role of LRRK2 in OL differentiation. Consistently, we found an alteration of myelin basic protein (MBP) striosomes in LRRK2 KO mouse brains and reduced levels of oligodendrocyte transcription factor 2 (Olig2) and Mbp in olig2:EGFP and mbp:RFP transgenic zebrafish embryos injected with lrrk2 morpholino (MO). Moreover, lrrk2 knock-down zebrafish exhibited a lower amount of nerve growth factor (Ngf) compared to control embryos, which represents a potent regulator of oligodendrogenesis and myelination. Overall, our findings indicate that LRRK2 controls OL differentiation, affecting the number of mature OLs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping