Tig1 regulates proximo-distal identity during salamander limb regeneration

Research output: Contribution to journalResearch articleContributedpeer-review



Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an awareness of their spatial location, a property termed positional identity. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/Rarres1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting Hoxa13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.


Original languageEnglish
Article number1141
JournalNature communications
Issue number1
Early online date3 Mar 2022
Publication statusPublished - Dec 2022

External IDs

PubMed 35241664
Mendeley 9bdd0207-074e-37b9-a728-c772b0cc5135
WOS 000764258100022
ORCID /0000-0001-9599-8632/work/142241739