Putting it all together: Current research by Hung et al. suggests an important role for epigenetic mechanisms in modulating Schwann cell activity in the research paper, " The Nucleosome Remodeling and Deacetylase Chromatin Remodeling (NuRD) Complex is Required for Peripheral Nerve Myelination".
Contextual Introduction: The process of myelination by Schwann cells is an important and timely activity within the peripheral nervous system, requiring careful coordination of gene expression and gene suppression. It is known that epigenetic mechanisms are responsible for modulating gene expression patterns in multiple types of glial cells. The research conducted by Hung et. al. aimed to explore the role of chromodomain helicase DNA-binding protein 4 (Chd4), the core catalytic subunit of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex in regulating Schwann cell myelination.
Experimental System:
For this study, researchers used mice as the model organism due to their known genomic sequence for easy manipulation and their translational value as a mammalian vertebrate with similar development as humans. To examine Schwann cells of the PNS, the researchers focused on the sciatic nerve for many of their experiments. Its large size allows for easy dissection and manipulation for detailed analysis.
The researchers used a variety of experimental techniques to address their topic, the first of which consisted of generating a conditional knockout mouse line, using Cre recombination to excise Chd4 in Schwann cells. With this transgenic line, the researchers could easily asses the differences between mutant Chd4 mice and control mice with respect to myelination.
Results:
Experimental System:
For this study, researchers used mice as the model organism due to their known genomic sequence for easy manipulation and their translational value as a mammalian vertebrate with similar development as humans. To examine Schwann cells of the PNS, the researchers focused on the sciatic nerve for many of their experiments. Its large size allows for easy dissection and manipulation for detailed analysis.
The researchers used a variety of experimental techniques to address their topic, the first of which consisted of generating a conditional knockout mouse line, using Cre recombination to excise Chd4 in Schwann cells. With this transgenic line, the researchers could easily asses the differences between mutant Chd4 mice and control mice with respect to myelination.
Results:
Experiment
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Findings
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Main Conclusions:
- Chd4 ablation clearly affected motor coordination in mice, producing abnormal reflexes and a progressive onset of motor function impairment in the hindlimbs.
- Chd4 plays a critical role in maintaining the timely induction of Schwann cell radial sorting, normal myelin sheath thickness, and cell cycle arrest.
- Chd4 itself exhibits bimodal capabilities in that it can both activate and
repress various genes involved in the myelination process
Figure 4: Summary of main conclusions. With Chd4 (left) shows normal myelination, balanced by coordinate expression and repression of pro-myelinating genes and immature Schwann cell genes respectively. Without Chd4 (right) shows abnormal myelination with the balance shifting toward an immature Schwann cell state due to the expression and repression of immature Schwann cell genes and pro-myelination genes respectively.
*These pro-myelination genes are those that are expressed only after the expression of specific positive regulators, which were shown to be equally present in both the control and mutant mice, suggesting that the activity of Chd4 is timely and acts independently of some positive regulators.
*These pro-myelination genes are those that are expressed only after the expression of specific positive regulators, which were shown to be equally present in both the control and mutant mice, suggesting that the activity of Chd4 is timely and acts independently of some positive regulators.