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Role of transcription factors in peripheral nerve regeneration
Smriti Patodia1, Gennadij Raivich
1Centre for Perinatal Brain Protection and Repair, University College London London, UK.
Abstract:
Following axotomy, the activation of multiple intracellular signaling cascades causes the expression of a cocktail of regeneration-associated transcription factors which interact with each other to determine the fate of the injured neurons. The nerve injury response is channeled through manifold and parallel pathways, integrating diverse inputs, and controlling a complex transcriptional output. Transcription factors form a vital link in the chain of regeneration, converting injury-induced stress signals into downstream protein expression via gene regulation. They can regulate the intrinsic ability of axons to grow, by controlling expression of whole cassettes of gene targets. In this review, we have investigated the functional roles of a number of different transcription factors - c-Jun, activating transcription factor 3, cAMP response element binding protein, signal transducer, and activator of transcription-3, CCAAT/enhancer binding proteins β and δ, Oct-6, Sox11, p53, nuclear factor kappa-light-chain-enhancer of activated B cell, and ELK3 - in peripheral nerve regeneration. Studies involving use of conditional mutants, microarrays, promoter region mapping, and different injury paradigms, have enabled us to understand their distinct as well as overlapping roles in achieving anatomical and functional regeneration after peripheral nerve injury.
Insights
Transcription factors are crucial for peripheral nerve regeneration after injury. This review details how these proteins regulate gene expression to promote axon growth and functional recovery.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Peripheral nerve injury triggers intracellular signaling cascades.
- These cascades lead to the expression of regeneration-associated transcription factors.
- Transcription factors are key regulators of gene expression during nerve repair.
Purpose of the Study:
- To review the functional roles of specific transcription factors in peripheral nerve regeneration.
- To elucidate the distinct and overlapping functions of these factors in neuronal repair.
- To understand how transcription factors mediate the cellular response to nerve injury.
Main Methods:
- Review of studies utilizing conditional mutants.
- Analysis of microarray data to identify gene expression changes.
- Promoter region mapping to understand transcription factor binding.
- Examination of various peripheral nerve injury paradigms.
Main Results:
- Identified multiple transcription factors (e.g., c-Jun, ATF3, CREB, STAT3, C/EBPβ, C/EBPδ, Oct-6, Sox11, p53, NF-κB, ELK3) involved in nerve regeneration.
- Demonstrated that these factors regulate gene expression critical for axon growth.
- Highlighted both unique and shared roles among these transcription factors in the regeneration process.
Conclusions:
- Transcription factors are vital mediators converting injury signals into regenerative protein expression.
- Understanding these factors' roles is essential for developing strategies to enhance peripheral nerve regeneration.
- The interplay of multiple transcription factors orchestrates successful anatomical and functional recovery after nerve injury.
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