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Development 2020 Feb 05;1473:. doi: 10.1242/dev.185496.
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The myeloid lineage is required for the emergence of a regeneration-permissive environment following Xenopus tail amputation.

Aztekin C , Hiscock TW , Butler R , De Jesús Andino F , Robert J , Gurdon JB , Jullien J .

Regeneration-competent vertebrates are considered to suppress inflammation faster than non-regenerating ones. Hence, understanding the cellular mechanisms 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 reduction in amputation-induced apoptosis levels in the myeloid lineage, which in turn promotes tissue remodelling, and ultimately leads to the relocalization of the regeneration-organizing cells responsible for progenitor proliferation. These cellular mechanisms 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.

PubMed ID: 31988186
PMC ID: PMC7033733
Article link: Development
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: arg1 ccl5 ccr2 cebpa csf1r g6pd gpr141 gpr34 hif1a il15 il16 il1b il6 il6r isyna1 lef1 mmp1 mmp13 mmp25 mmp3 mmp7 mmp9.1 mmp9.2 mpo myh6 nadk nfkb1 nos3 ntsr1 pdgfb pdk1 pfkfb1 pfkfb4 prkaa1 ptgs2 scarb1 scarb2 slc2a2 slc2a3 slc2a6 slc2a8 slurp1l spi1 spib tgfb1 timp2 tlr4 tlr5 tnf tp63 tyr ulk1
GO keywords: inflammatory cell apoptotic process [+]
Antibodies: GFP Ab16 Tp63 Ab2

Article Images: [+] show captions
References [+] :
Adams, H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration. 2007, Pubmed, Xenbase