Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation |
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| Authors: | Chanchao Lorthongpanich Daniel M. Messerschmidt Siew Wee Chan Wanjin Hong Barbara B. Knowles Davor Solter |
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| Affiliation: | 1.Mammalian Development Laboratory, Institute of Medical Biology, Singapore 138648, Singapore;;2.Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, Singapore 138648, Singapore;;3.Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore;;4.Duke University-National University of Singapore (Duke-NUS) Graduate Medical School, Singapore 169857, Singapore |
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| Abstract: | Cellular localization of the Yes-associated protein (YAP) is dependent on large tumor suppressor (LATS) kinase activity and initiates lineage specification in the preimplantation embryo. We temporally reduced LATS activity to disrupt this early event, allowing its reactivation at later stages. This interference resulted in an irreversible lineage misspecification and aberrant polarization of the inner cell mass (ICM). Complementation experiments revealed that neither epiblast nor primitive endoderm can be established from these ICMs. We therefore conclude that precisely timed YAP localization in early morulae is essential to prevent trophectoderm marker expression in, and lineage specification of, the ICM. |
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| Keywords: | Hippo pathway LATS inner cell mass trophectoderm lineage specification |
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