ROCK and RHO Playlist for Preimplantation Development: Streaming to HIPPO Pathway and Apicobasal Polarity in the First Cell Differentiation

Abstract

In placental mammalian development, the first cell differentiation produces two distinct lineages that emerge according to their position within the embryo: the trophectoderm (TE, placenta precursor) differentiates in the surface, while the inner cell mass (ICM, fetal body precursor) forms inside. Here, we discuss how such position-dependent lineage specifications are regulated by the RHOA subfamily of small GTPases and RHO-associated coiled-coil kinases (ROCK). Recent studies in mouse show that activities of RHO/ROCK are required to promote TE differentiation and to concomitantly suppress ICM formation. RHO/ROCK operate through the HIPPO signaling pathway, whose cell position-specific modulation is central to establishing unique gene expression profiles that confer cell fate. In particular, activities of RHO/ROCK are essential in outside cells to promote nuclear localization of transcriptional co-activators YAP/TAZ, the downstream effectors of HIPPO signaling. Nuclear localization of YAP/TAZ depends on the formation of apicobasal polarity in outside cells, which requires activities of RHO/ROCK. We propose models of how RHO/ROCK regulate lineage specification and lay out challenges for future investigations to deepen our understanding of the roles of RHO/ROCK in preimplantation development. Finally, as RHO/ROCK may be inhibited by certain pharmacological agents, we discuss their potential impact on human preimplantation development in relation to fertility preservation in women.

HIPPO signaling resolves embryonic cell fate conflicts during establishment of pluripotency in vivo

“…Several direct and indirect targets of ROCK1/2 kinases in the early embryo have been described ( Alarcon and Marikawa, 2018 ; Shi et al, 2017 ). Among these is YAP1, a transcriptional partner of TEAD4 ( Nishioka et al, 2009 ), since ROCK activity is required for the nuclear localization of YAP1 ( Kono et al, 2014 ).…”

A tale of two cell-fates: role of the Hippo signaling pathway and transcription factors in early lineage formation in mouse preimplantation embryos

“…Several studies have also shown that Rho and Rho-associated coiled-coil kinases 1 and 2 (ROCK1 and ROCK2) are necessary for lineage formation by negatively regulating the Hippo pathway ( Kono et al , 2014 ; Shi et al , 2017 ; Alarcon and Marikawa, 2018 ). ROCK is activated by Rho small GTPases and then it phosphorylates a variety of targets involved in modulation of cellular processes such as cell polarity and gene expression ( Amano et al , 2010 ; Julian and Olson, 2014 ).…”

Role of Hippo-YAP1/TAZ pathway and its crosstalk in cardiac biology

“…YAP1/TAZ activation by the Gα 12/13 -RhoA-ROCK axis can promote endothelial cell sprouting, facilitate vascular smooth muscle cell (VSMC) migration and proliferation, and may participate in embryonic vascular development 73 . Furthermore, Rho-ROCK axis promote trophectoderm differentiation and inhibit the formation of the inner cell mass through enhanced YAP1 nuclear localization 84 . Thus, the Gα 12/13 -RhoA-ROCK axis may participate in YAP1/TAZ-mediated cardiac biology.…”