title: TEAD4 establishes the energy homeostasis essential for blastocoel formation.
abstract: It has been suggested that during mouse preimplantation development, the zygotically expressed transcription factor TEAD4 is essential for specification of the trophectoderm lineage required for producing a blastocyst. Here we show that blastocysts can form without TEAD4 but that TEAD4 is required to prevent oxidative stress when blastocoel formation is accompanied by increased oxidative phosphorylation that leads to the production of reactive oxygen species (ROS). Both two-cell and eight-cell Tead4(-/-) embryos developed into blastocysts when cultured under conditions that alleviate oxidative stress, and Tead4(-/-) blastocysts that formed under these conditions expressed trophectoderm-associated genes. Therefore, TEAD4 is not required for specification of the trophectoderm lineage. Once the trophectoderm was specified, Tead4 was not essential for either proliferation or differentiation of trophoblast cells in culture. However, ablation of Tead4 in trophoblast cells resulted in reduced mitochondrial membrane potential. Moreover, Tead4 suppressed ROS in embryos and embryonic fibroblasts. Finally, ectopically expressed TEAD4 protein could localize to the mitochondria as well as to the nucleus, a property not shared by other members of the TEAD family. These results reveal that TEAD4 plays a crucial role in maintaining energy homeostasis during preimplantation development.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-2753, USA. KanekoK@mail.nih.gov
authors.forename: Kotaro J
authors.initials: KJ
authors.lastname: Kaneko
authors.forename: Melvin L
authors.initials: ML
authors.lastname: DePamphilis
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D000091262:TEA Domain Transcription Factors; C101204:Tead4 protein, mouse; D014157:Transcription Factors
keywords: Anti-oxidant; Blastocoel; Blastocyst; Mouse; Oxidative stress; Tead4; Trophectoderm
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