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

B Béryl Laplace-Builhé (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM) G Gautier Tejedor (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM) J Jholy De La Cruz (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM) A Audrey Barthelaix (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM) F Frédéric Marmigère (Institute of Functional Genomics of Lyon, CNRS, École Normale Supérieure) D Dora Sapède (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM) S Sarah Bahraoui (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM) L Lucie Diouloufet (Institute of Neurosciences of Montpellier, University of Montpellier, INSERM) S Stéphanie Ventéo (Institute of Neurosciences of Montpellier, University of Montpellier, INSERM) J Jérôme Collignon (Université Paris Cité, CNRS, Institut Jacques Monod) C Christian Jorgensen (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM) F Farida Djouad (Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM)

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, Wnt1 and Foxd3 , 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.

Article Details

Volume / Issue Vol. 122, Issue 52
Published December 30, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (12)

B

Béryl Laplace-Builhé

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM

G

Gautier Tejedor

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM

J

Jholy De La Cruz

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM

A

Audrey Barthelaix

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM

F

Frédéric Marmigère

Institute of Functional Genomics of Lyon, CNRS, École Normale Supérieure

D

Dora Sapède

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM

S

Sarah Bahraoui

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM

L

Lucie Diouloufet

Institute of Neurosciences of Montpellier, University of Montpellier, INSERM

S

Stéphanie Ventéo

Institute of Neurosciences of Montpellier, University of Montpellier, INSERM

J

Jérôme Collignon

Université Paris Cité, CNRS, Institut Jacques Monod

C

Christian Jorgensen

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM

F

Farida Djouad

Institute for Regenerative Medicine and Biotherapies, University of Montpellier, INSERM