Foxm1 regulates neural progenitor fate during spinal cord regeneration

EMBO Reports, 2021 · DOI: 10.15252/embr.202050932 · Published: August 24, 2021

Neurology Genetics Regenerative Medicine & Stem Cells

Simple Explanation

Xenopus tadpoles can regenerate their tails, including the spinal cord, after amputation. This study investigates the tissue-specific responses of the spinal cord during this regeneration process, focusing on the role of specific genes. The researchers identified Foxm1, a transcription factor, as essential for spinal cord regeneration. Surprisingly, Foxm1 does not control how fast neural progenitors divide but instead regulates what they become after dividing. In tadpoles lacking Foxm1, there were fewer neurons in the regenerating spinal cord. This suggests that the creation of new neurons is important for the spinal cord to regenerate properly.

Study Duration

7 days

Participants

Xenopus tropicalis tadpoles

Evidence Level

Molecular Biology, scRNA-seq, CRISPR/Cas9 knockout

Key Findings

1
Foxm1 is specifically expressed in the regenerating spinal cord of Xenopus tadpoles, peaking at 3 days post-amputation.
2
Foxm1 is required for spinal cord regeneration, as foxm1−/− tadpoles show a significantly reduced rate of regeneration compared to wild-type tadpoles.
3
Foxm1 does not affect the overall length of the cell cycle of neural progenitors but regulates their fate, promoting neuronal differentiation rather than self-renewal.

Research Summary

This study investigates the role of Foxm1, a transcription factor, in spinal cord regeneration in Xenopus tropicalis tadpoles using bulk and single-cell RNA sequencing. The research finds that Foxm1 is specifically expressed in the regenerating spinal cord and is essential for proper regeneration, influencing the fate of neural progenitors to differentiate into neurons. Unlike its previously known functions, Foxm1 does not control the rate of progenitor proliferation or the length of the cell cycle in this context, suggesting a cell cycle-independent role in promoting neuronal differentiation during regeneration.

Practical Implications

Regenerative Medicine

Understanding the specific role of Foxm1 in promoting neuronal differentiation could provide new targets for enhancing spinal cord regeneration in species with limited regenerative capabilities, including mammals.

Cell Fate Regulation

The study reveals a cell cycle-independent function of Foxm1 in determining cell fate, specifically promoting neuronal differentiation, which challenges previous understandings of its role primarily as a cell cycle regulator.

Spinal Cord Injury Treatment

Identifying the signals and regulatory networks that enable Foxm1 to drive neuronal differentiation may lead to new strategies for improving functional recovery after spinal cord injuries by encouraging the formation of new neurons.

Study Limitations

1
The number of cells and the depth of sequencing did not allow us to unambiguously determine the identity of progenitors and neurons subtypes
2
The study focuses on Xenopus tadpoles, and the findings may not be directly transferable to mammalian systems.
3
The precise upstream signals regulating Foxm1 expression during regeneration are not fully elucidated, requiring further investigation.

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