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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:91652 |
| Date | 04 June 2024 |
| Creators | Oliveira, Catarina R., Knapp, Dunja, Elewa, Ahmed, Gerber, Tobias, Gonzalez Malagon, Sandra G., Gates, Phillip B., Walters, Hannah E., Petzold, Andreas, Arce, Hernan, Cordoba, Rodrigo C., Subramanian, Elaiyaraja, Chara, Osvaldo, Tanaka, Elly M., Simon, András, Yun, Maximina H. |
| Publisher | Nature Publishing Group UK |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2041-1723, 1141, 10.1038/s41467-022-28755-1, info:eu-repo/grantAgreement/European Commission/FP7 | SP2 | ERC/294324//A Cross Species Approach to Understand the Mechanism and Evolution of Limb Regeneration Capacity/REGENERATEACROSS, info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/FZT 111: Zentrum für Regenerative Therapien Dresden (CRTD)/22137416/, info:eu-repo/grantAgreement/Deutsche Forschungsgemeinschaft/Zelluläre und molekulare Grundlagen der de novo Regeneration des Thymus/450807335/ |
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