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Melzer, M.K.* ; Schirge, S. ; Gout, J.* ; Arnold, F.* ; Srinivasan, D.* ; Burtscher, I. ; Allgöwer, C.* ; Mulaw, M.* ; Zengerling, F.* ; Günes, C.* ; Lickert, H. ; Christoffels, V.M.* ; Liebau, S.* ; Wagner, M.* ; Seufferlein, T.* ; Bolenz, C.* ; Moon, A.M.* ; Perkhofer, L.* ; Kleger, A.*

TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration.

BMC Biol. 21:55 (2023)

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BACKGROUND: The reactivation of genetic programs from early development is a common mechanism for injury-induced organ regeneration. T-box 3 (TBX3) is a member of the T-box family of transcription factors previously shown to regulate pluripotency and subsequent lineage commitment in a number of tissues, including limb and lung. TBX3 is also involved in lung and heart organogenesis. Here, we provide a comprehensive and thorough characterization of TBX3 and its role during pancreatic organogenesis and regeneration. RESULTS: We interrogated the level and cell specificity of TBX3 in the developing and adult pancreas at mRNA and protein levels at multiple developmental stages in mouse and human pancreas. We employed conditional mutagenesis to determine its role in murine pancreatic development and in regeneration after the induction of acute pancreatitis. We found that Tbx3 is dynamically expressed in the pancreatic mesenchyme and epithelium. While Tbx3 is expressed in the developing pancreas, its absence is likely compensated by other factors after ablation from either the mesenchymal or epithelial compartments. In an adult model of acute pancreatitis, we found that a lack of Tbx3 resulted in increased proliferation and fibrosis as well as an enhanced inflammatory gene programs, indicating that Tbx3 has a role in tissue homeostasis and regeneration. CONCLUSIONS: TBX3 demonstrates dynamic expression patterns in the pancreas. Although TBX3 is dispensable for proper pancreatic development, its absence leads to altered organ regeneration after induction of acute pancreatitis.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Acute Pancreatitis ; Embryonic Development ; Organ Regeneration ; Pancreatic Development ; Tbx3; Gene-expression; Mammary-gland; Stem-cells; Lef1; Rna; Program; Catenin; Lineage; Protein; Cancer

e-ISSN 1741-7007

Journal BMC Biology

Quellenangaben Volume: 21, Issue: 1, Article Number: 55

Publisher BioMed Central

Publishing Place Campus, 4 Crinan St, London N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Stem Cell Research (ISF)

Grants German Center for Diabetes Research (DZD)
Helmholtz Association
DFG
German Cancer Aid
Deutsche Forschungsgemeinschaft (DFG) "Sachbeihilfe"
Projekt DEAL