Abstract
Regeneration-competent vertebrates are considered to suppress inflammation faster than non-regenerating ones. Hence, understanding the cellularmechanisms affected by immune cells and inflammation can help develop strategies to promote tissue repair and regeneration. Here, we took advantage of naturally occurring tail regeneration-competent and -incompetent developmental stages of Xenopus tadpoles. We first establish the essential role of the myeloid lineage for tail regeneration in the regeneration-competent tadpoles. We then reveal that upon tail amputation there is a myeloid lineage-dependent change in amputationinduced apoptosis levels, which in turn promotes tissue remodelling, and ultimately leads to the relocalization of the regeneration-organizing cells responsible for progenitor proliferation. These cellularmechanisms failed to be executed in regeneration-incompetent tadpoles. We demonstrate that regeneration incompetency is characterized by inflammatory myeloid cells whereas regeneration competency is associated with reparative myeloid cells. Moreover, treatment of regeneration-incompetent tadpoles with immune-suppressing drugs restores myeloid lineage-controlled cellular mechanisms. Collectively, our work reveals the effects of differential activation of the myeloid lineage on the creation of a regeneration-permissive environment and could be further exploited to devise strategies for regenerative medicine purposes.
Original language | English |
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Article number | 185496 |
Number of pages | 10 |
Journal | Development |
Volume | 147 |
Issue number | 3 |
Early online date | 27 Jan 2020 |
DOIs | |
Publication status | Published - 5 Feb 2020 |
Externally published | Yes |
Bibliographical note
Acknowledgements: The transgenic testes used in this study and pTransgenesis vectors were obtained from the European Xenopus Resource Centre, curated with funding from the Wellcome Trust/BBSRC, and maintained by the University of Portsmouth, School of Biological Sciences. The CFP-NTR construct was provided by J. Mumm and M. Zuber. We thank H. Ma for use of their stereoscopes. We thank R. Jones-Green for excellent animal care. We thank E. Rawlins, B. Simons and B. Steventon for their critical reading of the manuscript.Keywords
- Inflammation
- Macrophages
- Myeloid lineage
- Neutrophils
- Tail regeneration
- Xenopus
- MACROPHAGES
- MODEL
- IDENTIFICATION
- HYALURONIC-ACID
- LIMB
- TRANSGENESIS
- AMPHIBIANS
- INFLAMMATION
- CELL