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Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse
Sangphil Oh1, Dongjun Lee, Tackhoon Kim
1National Research Laboratory of Molecular Genetics, Department of Biological Science, KAIST, Daejeon 305-701, South Korea.
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.
Insights
Mammalian sterile 20-like kinases 1 and 2 (Mst1 and Mst2) are crucial for early mouse development. Loss of both Mst1 and Mst2 leads to embryonic lethality due to severe placental and developmental defects.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Cell Biology
Background:
- Mammalian sterile 20-like kinases 1 and 2 (Mst1 and Mst2) are serine/threonine kinases.
- These kinases are known to be involved in regulating cell proliferation and cell death.
- The specific physiological roles of Mst1 and Mst2 in vivo, particularly during early development, were not fully understood.
Purpose of the Study:
- To investigate the essential physiological functions of Mst1 and Mst2 during mammalian development.
- To determine the consequences of combined Mst1 and Mst2 deficiency in mice.
- To elucidate the roles of Mst1 and Mst2 in embryonic and placental development.
Main Methods:
- Generation of Mst1 and Mst2 knockout mice, including single and double mutants.
- Phenotypic analysis of heterozygous and homozygous Mst1/Mst2 mutant mice.
- Detailed examination of embryonic and placental development, including vascular patterning, hematopoiesis, cell proliferation, and apoptosis.
Main Results:
- Mst1(-/-) and Mst2(-/-) mice were viable and fertile, indicating functional redundancy.
- Mice lacking both Mst1 and Mst2 (Mst1(-/-); Mst2(-/-)) exhibited embryonic lethality around embryonic day 8.5.
- These double knockout embryos showed severe growth retardation, failed placental development, impaired vascular patterning, disrupted primitive hematopoiesis, increased apoptosis, and disorganized cell proliferation.
Conclusions:
- Both Mst1 and Mst2 kinases are essential for early mouse embryonic development.
- These kinases play critical roles in regulating placental formation, embryonic vascularization, and primitive hematopoiesis.
- Mst1 and Mst2 are vital for maintaining cell proliferation and survival during early embryogenesis.
