Tig1 regulates proximo-distal identity during salamander limb regeneration

Catarina R. Oliveira, Dunja Knapp (), Ahmed Elewa, Tobias Gerber, Sandra G. Gonzalez Malagon, Phillip B. Gates, Hannah E. Walters, Andreas Petzold, Hernan Arce, Rodrigo C. Cordoba, Elaiyaraja Subramanian, Osvaldo Chara, Elly M. Tanaka, András Simon and Maximina H. Yun ()
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Catarina R. Oliveira: Technische Universität Dresden, CRTD/Center for Regenerative Therapies Dresden
Dunja Knapp: Technische Universität Dresden, CRTD/Center for Regenerative Therapies Dresden
Ahmed Elewa: Department of Cell and Molecular Biology, Karolinska Institute
Tobias Gerber: European Molecular Biology Laboratory (EMBL)
Sandra G. Gonzalez Malagon: University College London
Phillip B. Gates: University College London
Hannah E. Walters: Technische Universität Dresden, CRTD/Center for Regenerative Therapies Dresden
Andreas Petzold: Technische Universität Dresden, CRTD/Center for Regenerative Therapies Dresden
Hernan Arce: National Scientific and Technical Research Council (CONICET) and University of La Plata
Rodrigo C. Cordoba: National Scientific and Technical Research Council (CONICET) and University of La Plata
Elaiyaraja Subramanian: Department of Cell and Molecular Biology, Karolinska Institute
Osvaldo Chara: National Scientific and Technical Research Council (CONICET) and University of La Plata
Elly M. Tanaka: Institute of Molecular Pathology, Vienna Biocenter
András Simon: Department of Cell and Molecular Biology, Karolinska Institute
Maximina H. Yun: Technische Universität Dresden, CRTD/Center for Regenerative Therapies Dresden

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-28755-1

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