TY - JOUR
T1 - TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration
AU - Melzer, Michael Karl
AU - Schirge, Silvia
AU - Gout, Johann
AU - Arnold, Frank
AU - Srinivasan, Dharini
AU - Burtscher, Ingo
AU - Allgöwer, Chantal
AU - Mulaw, Medhanie
AU - Zengerling, Friedemann
AU - Günes, Cagatay
AU - Lickert, Heiko
AU - Christoffels, Vincent M.
AU - Liebau, Stefan
AU - Wagner, Martin
AU - Seufferlein, Thomas
AU - Bolenz, Christian
AU - Moon, Anne M.
AU - Perkhofer, Lukas
AU - Kleger, Alexander
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Acute pancreatitis
KW - Embryonic development
KW - Organ regeneration
KW - Pancreatic development
KW - TBX3
UR - http://www.scopus.com/inward/record.url?scp=85150752228&partnerID=8YFLogxK
U2 - 10.1186/s12915-023-01553-x
DO - 10.1186/s12915-023-01553-x
M3 - Article
C2 - 36941669
AN - SCOPUS:85150752228
SN - 1741-7007
VL - 21
JO - BMC Biology
JF - BMC Biology
IS - 1
M1 - 55
ER -