PUBLICATION
Fmrp regulates oligodendrocyte lineage cell specification and differentiation
- Authors
- Doll, C.A., Scott, K., Appel, B.
- ID
- ZDB-PUB-210611-5
- Date
- 2021
- Source
- Glia 69(10): 2349-2361 (Journal)
- Registered Authors
- Appel, Bruce
- Keywords
- FMRP, OPC, differentiation, oligodendrocyte, specification
- MeSH Terms
-
- Animals
- Cell Differentiation/physiology
- Cell Lineage
- Female
- Fragile X Mental Retardation Protein*/genetics
- Fragile X Mental Retardation Protein*/metabolism
- Motor Neurons/metabolism
- Oligodendroglia/metabolism
- Pregnancy
- RNA-Binding Proteins*
- Zebrafish*/metabolism
- Zebrafish Proteins*
- PubMed
- 34110049 Full text @ Glia
Citation
Doll, C.A., Scott, K., Appel, B. (2021) Fmrp regulates oligodendrocyte lineage cell specification and differentiation. Glia. 69(10):2349-2361.
Abstract
Neurodevelopment requires the precise integration of a wide variety of neuronal and glial cell types. During early embryonic development, motor neurons and then oligodendrocyte precursor cells (OPCs) are specified from neural progenitors residing in the periventricular pMN progenitor domain of the spinal cord. Following gliogenesis, OPCs can differentiate as oligodendrocytes (OLs)-the myelinating glial cells of the central nervous system-or remain as OPCs. To generate unique cell types capable of highly divergent functions, these specification and differentiation events require specialized gene expression programs. RNA binding proteins (RBPs) regulate mRNA localization and translation in the developing nervous system and are linked to many neurodevelopmental disorders. One example is Fragile X syndrome (FXS), caused by the loss of the RBP fragile X mental retardation protein (FMRP). Importantly, infants with FXS have reduced white matter and we previously showed that zebrafish Fmrp is autonomously required in OLs to promote myelin sheath growth. We now find that Fmrp regulates cell specification in pMN progenitor cells such that fmr1 mutant zebrafish generate fewer motor neurons and excess OPCs. Fmrp subsequently promotes differentiation of OPCs, leading to fewer differentiating OLs in the developing spinal cord of fmr1 larvae. Although the early patterning of spinal progenitor domains appears largely normal in fmr1 mutants during early embryogenesis, Shh signaling is greatly diminished. Taken together, these results suggest cell stage-specific requirements for Fmrp in the specification and differentiation of oligodendrocyte lineage cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping