Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression

Atsushi Suzuki, Sayaka Sekiya, Dirk Büscher, Juan Carlos Izpisúa Belmonte, Hideki Taniguchi

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Although the T-box family of transcription factors function in many different tissues, their role in liver development is unknown. Here we show that Tbx3, the T-box gene that is mutated in human ulnar-mammary syndrome, is specifically expressed in multipotent hepatic progenitor cells, 'hepatoblasts', isolated from the developing mouse liver. Tbx3-deficient hepatoblasts presented severe defects in proliferation as1well as uncontrollable hepatobiliary lineage segregation, including the promotion of cholangiocyte (biliary epithelial cell) differentiation, which thereby caused abnormal liver development. Deletion of Tbx3 resulted in the increased expression of the tumor suppressor p19ARF (Cdkn2a), which in turn induced a growth arrest in hepatoblasts and activated a program of cholangiocyte differentiation. Thus, Tbx3 plays a crucial role in controlling hepatoblast proliferation and cell-fate determination by suppressing p19ARF expression and thereby promoting liver organogenesis.

Original languageEnglish
Pages (from-to)1589-1595
Number of pages7
JournalDevelopment
Volume135
Issue number9
DOIs
Publication statusPublished - May 1 2008

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Hepatocytes
Stem Cells
Liver
Organogenesis
Cell Differentiation
Transcription Factors
Epithelial Cells
Cell Proliferation
Growth
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Cell Biology

Cite this

Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression. / Suzuki, Atsushi; Sekiya, Sayaka; Büscher, Dirk; Belmonte, Juan Carlos Izpisúa; Taniguchi, Hideki.

In: Development, Vol. 135, No. 9, 01.05.2008, p. 1589-1595.

Research output: Contribution to journalArticle

Suzuki, Atsushi ; Sekiya, Sayaka ; Büscher, Dirk ; Belmonte, Juan Carlos Izpisúa ; Taniguchi, Hideki. / Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression. In: Development. 2008 ; Vol. 135, No. 9. pp. 1589-1595.
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