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Home et al. (1) propose a provocative model of cell fate specification in preimplantation embryos, in which regulated nuclear localization of Tead4 controls trophectoderm vs. inner cell mass (ICM) formation, whereas its coactivator protein, Yap, is present in all nuclei. This model is inconsistent with our model in which position-dependent Hippo/Lats signaling regulates nuclear versus cytoplasmic Yap distribution whereas Tead4 is constitutively nuclear (2). Our model is consistent with the canonical Hippo signaling pathways conserved from flies to mammals (3). Because both models are highly dependent on the antibodies used for Tead4 and Yap, we repeated the immunostaining experiments involving preimplantation embryos with the antibodies used by Home et al. (1). We first examined Tead4 protein distribution in preimplantation embryos using the anti-Tead4 antibody described in the study of Home et al. (1) (ab58310; Abcam). Tead4 signals were detected in the nuclei of all blastomeres, including the inner cells of 16- and 32-cell–stage embryos (Fig. 1 A–C). Position-dependent differences in signal intensities gradually became evident from the 32-cell stage onward (Fig. 1 B and C), leading …

Tead4 is constitutively nuclear, while nuclear vs. cytoplasmic Yap distribution is regulated in preimplantation mouse embryos