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PMID:19786569

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Citation

Oh, S, Lee, D, Kim, T, Kim, TS, Oh, HJ, Hwang, CY, Kong, YY, Kwon, KS and Lim, DS (2009) Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse. Mol. Cell. Biol. 29:6309-20

Abstract

Mammalian sterile 20-like kinases 1 and 2 (Mst1 and Mst2, respectively) are potent serine/threonine kinases that are involved in cell proliferation and cell death. To investigate the physiological functions of Mst1 and Mst2, we generated Mst1 and Mst2 mutant mice. Mst1(-/-) and Mst2(-/-) mice were viable and fertile and developed normally, suggesting possible functional overlaps between the two genes. A characterization of heterozygous and homozygous combinations of Mst1 and Mst2 mutant mice showed that mice containing a single copy of either gene underwent normal organ development; however, Mst1(-/-); Mst2(-/-) mice lacking both Mst1 and Mst2 genes started dying in utero at approximately embryonic day 8.5. Mst1(-/-); Mst2(-/-) mice exhibited severe growth retardation, failed placental development, impaired yolk sac/embryo vascular patterning and primitive hematopoiesis, increased apoptosis in placentas and embryos, and disorganized proliferating cells in the embryo proper. These findings indicate that both Mst1 and Mst2 kinases play essential roles in early mouse development, regulating placental development, vascular patterning, primitive hematopoiesis, and cell proliferation and survival.

Links

PubMed PMC2786698 Online version:10.1128/MCB.00551-09

Keywords

Animals; Apoptosis; Cell Proliferation; Embryo, Mammalian/blood supply; Embryo, Mammalian/cytology; Embryo, Mammalian/enzymology; Embryonic Development; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Hematopoiesis; Mice; Mice, Knockout; Placenta/abnormalities; Placenta/enzymology; Pregnancy; Protein-Serine-Threonine Kinases/deficiency; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Signal Transduction

Significance

Annotations

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

MOUSE:STK3

acts_upstream_of_or_within

GO:0001841: neural tube formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

  • results_in_formation_of:(EMAPA:16164)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

  • regulates_o_occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0007417: central nervous system development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

  • results_in_development_of:(EMAPA:16470)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0003157: endocardium development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

  • results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0060706: cell differentiation involved in embryonic placenta development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

  • occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

  • occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0001841: neural tube formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

  • results_in_formation_of:(EMAPA:16164)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0001569: branching involved in blood vessel morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

  • occurs_in:(EMAPA:16370)|occurs_in:(EMAPA:16104)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

  • regulates_o_occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0007417: central nervous system development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

  • results_in_development_of:(EMAPA:16470)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0003157: endocardium development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

  • results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0060706: cell differentiation involved in embryonic placenta development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

  • occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

  • occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0060706: cell differentiation involved in embryonic placenta development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

regulates_o_occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0007417: central nervous system development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

results_in_development_of:(EMAPA:16470)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0003157: endocardium development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0001569: branching involved in blood vessel morphogenesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

occurs_in:(EMAPA:16370)|occurs_in:(EMAPA:16104)

Seeded From UniProt

complete

MOUSE:STK4

acts_upstream_of_or_within

GO:0001841: neural tube formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1928487

P

results_in_formation_of:(EMAPA:16164)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

regulates_o_occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0007417: central nervous system development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

results_in_development_of:(EMAPA:16470)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0003157: endocardium development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

results_in_development_of:(EMAPA:16105)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0001841: neural tube formation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

results_in_formation_of:(EMAPA:16164)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0060215: primitive hemopoiesis

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

occurs_in:(EMAPA:16042)

Seeded From UniProt

complete

MOUSE:STK3

acts_upstream_of_or_within

GO:0060706: cell differentiation involved in embryonic placenta development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1929004

P

occurs_in:(EMAPA:16042)

Seeded From UniProt

complete


See also

References

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