Fish species, such as zebrafish (Danio rerio), can regenerate their appendages after amputation through the formation of a heterogeneous cellular structure named blastema. Here, by combining live imaging of triple transgenic zebrafish embryos and single-cell RNA sequencing we established a detailed cell atlas of the regenerating caudal fin in zebrafish larvae. We confirmed the presence of macrophage subsets that govern zebrafish fin regeneration, and identified a foxd3-positive cell population within the regenerating fin. Genetic depletion of these foxd3-positive neural crest-derived cells (NCdC) showed that they are involved in blastema formation and caudal fin regeneration. Finally, chemical inhibition and transcriptomic analysis demonstrated that these foxd3-positive cells regulate macrophage recruitment and polarization through the NRG1/ErbB pathway. Here, we show the diversity of the cells required for blastema formation, identify a discrete foxd3-positive NCdC population, and reveal the critical function of the NRG1/ErbB pathway in controlling the dialogue between macrophages and NCdC.
Bibliographical noteFunding Information:
This work was supported by Inserm and University of Montpellier. We thank the MRI facility for their assistance, T. Sauka-Spengler (University of Oxford, United Kingdom) for shipping the Tg(foxd3-mcherry)ct110 zebrafish line, M. Bagnat for shipping Tg(rcn3:gal4/UAS:mCherry) line. A. Kawakami (Tokyo Institute of Technology, Japan) for the junbl plasmid, K. Poss (Duke University Medical Center, USA) for the nrg1 plasmid, R. Kelsh (University of Bath, United Kingdom) for the Fkd6in situ hybridization plasmid. MP and DS acknowledge financial support from the France Génomique National infrastructure, funded as part of “Investissement d’avenir” programme managed by the Agence Nationale pour la Recherche (contract ANR-10-INBS-09). We also thank the Zebrafish facility of the University of Montpellier, the MRI facility for their assistance and the CARTIGEN platform.
© 2021, The Author(s).