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PMID:18356246

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Citation

Suzuki, A, Sekiya, S, Büscher, D, Izpisúa Belmonte, JC and Taniguchi, H (2008) Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression. Development 135:1589-95

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 as well 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 p19(ARF) (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 p19(ARF) expression and thereby promoting liver organogenesis.

Links

PubMed Online version:10.1242/dev.016634

Keywords

Animals; Cell Differentiation/physiology; Cell Proliferation; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p16/biosynthesis; Liver/cytology; Liver/embryology; Mice; Multipotent Stem Cells/cytology; Multipotent Stem Cells/physiology; T-Box Domain Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TBX3

involved_in

GO:0061017: hepatoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3769504

P

Seeded From UniProt

complete

MOUSE:TBX3

involved_in

GO:0019827: stem cell population maintenance

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3769504

P

Seeded From UniProt

complete

MOUSE:TBX3

involved_in

GO:2000648: positive regulation of stem cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3769504

P

Seeded From UniProt

complete

MOUSE:TBX3

involved_in

GO:2000737: negative regulation of stem cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3769504

P

Seeded From UniProt

complete

MOUSE:TBX3

involved_in

GO:0072089: stem cell proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3769504

P

Seeded From UniProt

complete

MOUSE:TBX3

involved_in

GO:0030857: negative regulation of epithelial cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3769504

P

Seeded From UniProt

complete


See also

References

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