Open AccessCrucial Role for Mst1 and Mst2 Kinases in Early Embryonic Development of the Mouse
Author(s) -
Sangphil Oh,
Dongjun Lee,
Tackhoon Kim,
Tae-Shin Kim,
Hyun Jung Oh,
Chae Young Hwang,
Young Yun Kong,
Kideok D. Kwon,
Dae–Sik Lim
Publication year - 2009
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00551-09
Subject(s) - biology , hippo signaling pathway , microbiology and biotechnology , kinase , embryonic stem cell , embryogenesis , yolk sac , embryo , genetics , gene
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 generatedMst1 andMst2 mutant mice.Mst1 −/− andMst2 −/− mice were viable and fertile and developed normally, suggesting possible functional overlaps between the two genes. A characterization of heterozygous and homozygous combinations ofMst1 andMst2 mutant mice showed that mice containing a single copy of either gene underwent normal organ development; however,Mst1 −/− ;Mst2 −/− mice lacking bothMst1 andMst2 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.