The role of angiomotin phosphorylation in the Hippo pathway during preimplantation mouse development

Abstract

The Hippo signaling pathway regulates a number of cellular events, including the control of cell fates in preimplantation mouse embryos. The inner and outer cells of the embryo show high and low levels of Hippo signaling, respectively. This position-dependent Hippo signaling promotes the specification of distinct cell fates. In a recent paper, we identified the molecular mechanism that controls Hippo signaling in preimplantation embryos. The junction-associated scaffold protein Angiomotin (Amot) plays a key role in this mechanism. At the adherens junctions of the inner cells, Amot activates the Hippo pathway by recruiting and activating the protein kinase large tumor suppressor (Lats). In contrast, Amot at the apical membrane of the outer cells suppresses Hippo signaling by interacting with F-actin. The phosphorylation of Amot inhibits its interaction with F-actin and activates Hippo signaling. We propose that Amot acts as a molecular switch for the Hippo pathway and links F-actin with Lats activity.

The Biology of YAP/TAZ: Hippo Signaling and Beyond

“…This event, directly or indirectly, may modulate YAP inhibition by AMOT (1,26,41,86). An intriguing possibility is that F-actin/AMOT and YAP/AMOT complexes may be alternative to each other such that loss of F-actin may promote AMOT association to YAP (56,87,132). Consistently, the phenotypes of AMOT and AMOTL2 deficiency in the early mouse embryo support a role of AMOTs as YAP inhibitors in Hippo pathway activation (86,115 …”

Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos

“…Because Amot is absent from the AJs, Lats is not activated and the Hippo pathway remains inactive. In Amot mutants, Amotl2 weakly activates the Hippo pathway in the outer cells, indicating that apically localized Amot suppresses Hippopathway activation by Amotl2 [83]. Therefore, Amot is involved in both positive and negative regulation of the Hippo pathway.…”

CDX2 is essential for cell proliferation and polarity in porcine blastocysts

“…Similarly, prolonged OCT4 expression in the TE is also observed in human (Cauffman et al, 2005) and bovine (van Eijk et al, 1999) embryos. Since CDX2 accumulation is primed by Hippo signaling in response to cell contact and positional information in mice (Hirate and Sasaki, 2014;Nishioka et al, 2009), it would be interesting to explore whether this signaling pathway exists in porcine embryos, as this knowledge would expand our mechanistic understanding of the various CDX2 expression patterns observed in mammalian embryos.…”