Localized EMT reprograms glial progenitors to promote spinal cord repair

Dev Cell, 2021 · DOI: 10.1016/j.devcel.2021.01.017 · Published: March 8, 2021

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This research compares spinal cord repair in zebrafish, which regenerate, and mammals, which form scars. The study identifies that zebrafish glia activate an epithelial-to-mesenchymal transition (EMT) gene program during regeneration, a process not seen in mammals. Researchers found that glial progenitors in zebrafish undergo EMT after spinal cord injury, and they pinpointed a gene regulatory network responsible for activating EMT and promoting regeneration. The findings suggest that mammalian glia lack this key EMT-driving network, which is crucial for reprogramming glial cells for regeneration after injury.

Study Duration

Not specified

Participants

Adult zebrafish of the Ekkwill, Tubingen, and AB strains

Evidence Level

Not specified

Key Findings

1
Pro-regenerative zebrafish glia activate an epithelial-to-mesenchymal transition (EMT) gene program, distinguishing them from mammalian glia.
2
Localized niches of glial progenitors in zebrafish undergo EMT after spinal cord injury.
3
An EMT-driving gene regulatory network, involving twist-mediated EMT, promotes glial bridging and functional spinal cord repair in zebrafish.

Research Summary

This study identified an essential EMT-driving gene regulatory network that regulates differential regenerative capacity between mammals and zebrafish after SC injury. At the center of glial bridging is a multi-nodal gene regulatory network that is necessary and sufficient to promote twist-mediated EMT, ctgf-dependent glial bridging, and functional SC repair. Domains of ventro-lateral ependymal progenitors reminiscent of the developing progenitor motor neuron (PMN) domain were shown to give rise to regenerating motor neurons in injured adult fish.

Practical Implications

Potential Therapeutic Targets

Identifying the EMT-driving gene regulatory network in zebrafish glia offers potential therapeutic targets to enhance regenerative capacity in mammalian spinal cord injuries.

Bridging Glial Cell Fate

Further investigation into bridging glial cell fate will springboard translational applications to improve bridging and regeneration in the mammalian CNS.

Hybrid Molecular Identity

Zebrafish bridging glia possess a hybrid molecular identity that combines increased EMT-mediated plasticity with an astrocyte-like cell identity.

Study Limitations

1
The study primarily focuses on zebrafish, and further research is needed to translate findings to mammalian systems.
2
The precise mechanisms of Yap activation in specific niches of progenitor cells warrant further investigation.
3
The study identifies a gene regulatory network, but the specific interactions and regulatory elements may require further detailed characterization.

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