Neural crest cell recruitment and reprogramming as central drivers of embryonic limb regeneration

Unlike regeneration-competent species, mammals lack epimorphic regeneration capacity, except for the most distal part of their digits. Here, we show that E10.5 mouse embryos can initiate regeneration of their forelimb bud (FB), but this capacity is lost by E12.5. Using comparative transcriptomics and in vivo lineage tracing approaches in the mouse embryo, we were able to identify a population of neural crest-derived cells (NCdCs) reexpressing early NC lineage molecular markers, <i>Wnt1</i> and <i>Foxd3</i>, specifically associated with regeneration at E10.5. Functional studies further reveal that these cells are required for FB regeneration and that the regenerative capacity lost in limb buds lacking NCdCs can be restored by exogenous transplantation of neural crest cells at E10.5. This work provides valuable information on the potential and prerequisites for regeneration in mammals.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-12-23
DOI
https://doi.org/10.1073/pnas.2519994122
Primary Topic
Developmental Biology and Gene Regulation
Type
article
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article

Neural crest cell recruitment and reprogramming as central drivers of embryonic limb regeneration

Béryl Laplace-Builhe, Audrey Barthelaix, Jérôme Collignon, Farida Djouad et al.
Proceedings of the National Academy of Sciences
Developmental Biology and Gene Regulation
article

Neural crest cell recruitment and reprogramming as central drivers of embryonic limb regeneration

Béryl Laplace-Builhe, Audrey Barthelaix, Jérôme Collignon, Farida Djouad, Gautier Téjédor, Sarah Bahraoui, Frédéric Marmigère, Christian Jørgensen, Stéphanie Ventéo, Lucie Diouloufet, Jholy De La Cruz, Dora Sapède
article en

Abstract

Unlike regeneration-competent species, mammals lack epimorphic regeneration capacity, except for the most distal part of their digits. Here, we show that E10.5 mouse embryos can initiate regeneration of their forelimb bud (FB), but this capacity is lost by E12.5. Using comparative transcriptomics and in vivo lineage tracing approaches in the mouse embryo, we were able to identify a population of neural crest-derived cells (NCdCs) reexpressing early NC lineage molecular markers, <i>Wnt1</i> and <i>Foxd3</i>, specifically associated with regeneration at E10.5. Functional studies further reveal that these cells are required for FB regeneration and that the regenerative capacity lost in limb buds lacking NCdCs can be restored by exogenous transplantation of neural crest cells at E10.5. This work provides valuable information on the potential and prerequisites for regeneration in mammals.

Proceedings of the National Academy of SciencesVol. 122(52)
École Normale Supérieure de Lyon (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), Centre Hospitalier Universitaire de Montpellier (FR), Institute for Regenerative Medicine & Biotherapy (FR), Institut Jacques Monod (FR), Institute for Neurosciences of Montpellier (FR)
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Developmental Biology and Gene Regulation
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Neural crest cell recruitment and reprogramming as central drivers of embryonic limb regeneration — Béryl Laplace-Builhe, Audrey Barthelaix, et al. · Proceedings of the National Academy of Sciences (2025) | TGRS Research Map | TGRS