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Updated: Feb 17, 2026

Controlled Semi-Automated Laser-Induced Injuries for Studying Spinal Cord Regeneration in Zebrafish Larvae
Published on: November 22, 2021
Mechanisms of spinal cord injury regeneration in zebrafish: a systematic review
Zeynab Noorimotlagh1, Mahla Babaie1, Mahdi Safdarian2
1Medical Student, Iran University of Medical Sciences, Sina Trauma and Surgery Research Center, Tehran, Iran.
Objectives:
To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish.
Materials And Methods:
Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software.
Results:
Wnt/ß-catenin signaling, L1.1, L1.2, Major vault protein (MVP), contactin-2 and High mobility group box1 (HMGB1) had positive promoting effects on axonal re-growth while Ptena had an inhibitory effect. Neurogenesis is stimulated by Wnt/ß-catenin signaling as well as HMGB1, but inhibited by Notch signaling. Glial cells proliferate in response to fibroblast growth factor (FGF) signaling and Lysophosphatidic acid (LPA). Furthermore, fgf signaling pathway causes glia bridge formation in favor of axonal regeneration. LPA and HMGB1 in acute phase stimulate inflammatory responses around injury and suppress regeneration. LPA also induces microglia activation and neuronal death in addition to glia cell proliferation, but prevents neurite sprouting.
Conclusion:
This study provides a comprehensive review of the known molecules and mechanisms in the current literature involved in the spinal cord injury (SCI) regeneration in zebrafish, in a time course manner. A better understanding of the whole determining mechanisms for the SCI regeneration should be considered as a main goal for future studies.
Insights
Zebrafish spinal cord regeneration involves molecular pathways like Wnt/ß-catenin and HMGB1 promoting axonal regrowth and neurogenesis. Understanding these mechanisms is key for future spinal cord injury (SCI) repair strategies.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Zebrafish models
Background:
- Spinal cord injuries (SCI) present significant challenges in functional recovery.
- Zebrafish exhibit remarkable spinal cord regeneration capabilities, making them a valuable model organism.
Purpose of the Study:
- To comprehensively review the molecular and cellular mechanisms underlying spinal cord regeneration in zebrafish.
- To elucidate the time-course of these regenerative processes.
Main Methods:
- Systematic literature search of PubMed and Scopus databases.
- Keywords included: Zebrafish, spinal cord injuries, regeneration, recovery of function.
- Mechanism mapping performed using Xmind software.
Main Results:
- Positive regulators of axonal regrowth: Wnt/ß-catenin, L1.1, L1.2, MVP, contactin-2, HMGB1. Inhibitory effect: Ptena.
- Neurogenesis stimulated by Wnt/ß-catenin and HMGB1; inhibited by Notch signaling.
- Glial proliferation induced by FGF and LPA signaling; FGF promotes glia bridge formation.
- Acute phase: LPA and HMGB1 stimulate inflammation, suppressing regeneration. LPA also induces microglia activation, neuronal death, and inhibits neurite sprouting.
Conclusions:
- This review consolidates current knowledge on zebrafish SCI regeneration mechanisms.
- A detailed understanding of these molecular and cellular events is crucial for advancing future SCI repair research.

