Knockdown of Lingo1b protein promotes myelination and oligodendrocyte differentiation in zebrafish
- Authors
- Yin, W., and Hu, B.
- ID
- ZDB-PUB-140102-9
- Date
- 2014
- Source
- Experimental neurology 241: 72-83 (Journal)
- Registered Authors
- Keywords
- Lingo1b, myelination, Olgodendrocyte, differentiation, zebrafish, multiple sclerosis
- MeSH Terms
-
- Age Factors
- Animals
- Animals, Genetically Modified
- Cell Differentiation/drug effects
- Cell Differentiation/genetics*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/drug effects
- Gene Expression Regulation, Developmental/genetics*
- Green Fluorescent Proteins/genetics
- Humans
- Larva
- Membrane Proteins/genetics*
- Membrane Proteins/metabolism
- Microscopy, Electron, Transmission
- Morpholinos/pharmacology
- Motor Activity/drug effects
- Motor Activity/genetics
- Motor Neurons/physiology
- Myelin Sheath/genetics
- Myelin Sheath/metabolism*
- Myelin Sheath/ultrastructure
- Nerve Tissue Proteins/genetics*
- Nerve Tissue Proteins/metabolism
- Oligodendroglia/drug effects
- Oligodendroglia/metabolism*
- Oligodendroglia/ultrastructure
- Phylogeny
- RNA, Messenger/metabolism
- Zebrafish
- Zebrafish Proteins/deficiency*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 24262204 Full text @ Exp. Neurol.
Demyelinating diseases include multiple sclerosis, which is a neurodegenerative disease characterized by immune attacks on the central nervous system (CNS), resulting in myelin sheath damage and axonal loss. Leucine-rich repeat and immunoglobulin domain-containing neurite outgrowth inhibitory protein (Nogo) receptor-interacting protein-1 (LINGO-1) have been identified as a negative regulator of oligodendrocytes differentiation. Targeted LINGO-1 inhibition promotes neuron survival, axon regeneration, oligodendrocyte differentiation, and remyelination in diverse animal models. Although studies in rodent models have extended our understanding of LINGO-1, its roles in neural development and myelination in zebrafish (Danio rerio) are not yet clear. In this study, we cloned the zebrafish homolog of the human LINGO-1 and found that lingo1b regulated myelination and oligodendrocyte differentiation. The expression of lingo1b started 1 (mRNA) and 2 (protein) days post-fertilization (dpf) in the CNS. Morpholino oligonucleotide knockdown of lingo1b resulted in developmental abnormalities, including less dark pigment, small eyes, and a curly spinal cord. The lack of lingo1b enhanced myelination and oligodendrocyte differentiation during embryogenesis. Furthermore, immunohistochemistry and movement analysis showed that lingo1b was involved in the axon development of primary motor neurons. These results suggested that Lingo1b protein functions as a negative regulator of myelination and oligodendrocyte differentiation during zebrafish development.