What is it about?

Mouse embryos can regrow amputated forelimb buds—but only for a short window. We found that neural crest cells are essential for this regrowth, gathering at the injury and reactivating early developmental genes. Adding these cells back can even restore regeneration, pointing to new ways to unlock tissue repair in mammals that normally can’t regrow limbs.

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Why is it important?

We identify neural crest–derived cells as essential drivers of limb bud regeneration in early mouse embryos. This is important because mammals generally cannot regrow limbs, and understanding the cells and genes required for regeneration could reveal the prerequisites for restoring regenerative capacity in mammals. Two key findings are that: a) neural crest cells are specifically required for forelimb bud regrowth at E10.5, and b) transplantation of these cells can rescue regeneration when it is normally lost.

Perspectives

Conducting this study was especially rewarding, as it allowed us to investigate, for the first time, the cellular and molecular mechanisms behind limb bud regeneration in mammalian embryos. Our findings highlight the crucial role of neural crest–derived cells and their unique ability to revert to an early developmental state. Beyond deepening our fundamental understanding, this work opens new avenues for exploring how regenerative programs might be reactivated in non-regenerative tissues, with potential implications for future regenerative medicine strategies.

Farida Djouad
Inserm

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This page is a summary of: Neural crest cell recruitment and reprogramming as central drivers of embryonic limb regeneration, Proceedings of the National Academy of Sciences, December 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2519994122.
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