AI Article Synopsis

  • - The study investigates the role of the zinc-finger protein ZFP488 in the development and repair of oligodendrocytes, which are cells responsible for myelination in the central nervous system.
  • - Researchers created a genetically modified mouse to understand ZFP488's role, finding that its absence led to delayed myelination during development and impaired recovery post-injury.
  • - Analysis showed that ZFP488 promotes the expression of genes necessary for myelination, indicating its critical role in regulating the differentiation of oligodendrocytes at various developmental stages.

Article Abstract

Oligodendrocyte myelination and remyelination after injury are intricately regulated by various intrinsic and extrinsic factors, including transcriptional regulators. Among these, the zinc-finger protein ZFP488 is an oligodendrocyte-enriched transcriptional regulator that promotes oligodendrocyte differentiation in the developing neural tube and in oligodendroglial cell lines. However, the specific in vivo genetic requirements for ZFP488 during oligodendrocyte development and remyelination have not been defined. To address this gap, we generated a lineage-traceable knock-out mouse line, wherein an reporter replaces the -coding region. Using these mice of either sex, we examined the dynamics of expression from the endogenous promoter in the developing central nervous system (CNS). We observed a unique expression pattern in the oligodendrocyte lineage, with expression particularly enriched in differentiated oligodendrocytes. ZFP488 loss resulted in delayed myelination in the developing CNS and impaired remyelination after demyelinating injury in the brain. Integrated transcriptomic and genomic profiling further revealed that ZFP488 loss decreased the expression of myelination-associated genes but not oligodendrocyte progenitor-associated genes, suggesting that ZFP488 serves as a positive regulator of myelination by regulating maturation programs. Thus, our genetic loss-of-function study revealed that ZFP488 regulates a stage-dependent differentiation program that controls the timing of CNS myelination and remyelination.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426379PMC
http://dx.doi.org/10.1523/JNEUROSCI.0141-24.2024DOI Listing

Publication Analysis

Top Keywords

myelination remyelination
12
zinc-finger protein
8
protein zfp488
8
zfp488 regulates
8
oligodendrocyte myelination
8
zfp488 loss
8
revealed zfp488
8
zfp488
7
oligodendrocyte
6
myelination
5

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!