A Comparative Analysis of Hippo Signaling Pathway Components during Murine and Bovine Early Mammalian Embryogenesis

Abstract

The time required for successful blastocyst formation varies among multiple species. The formation of a blastocyst is governed by numerous molecular cell signaling pathways, such as the Hippo signaling pathway. The Hippo signaling pathway is initiated by increased cell–cell contact and via apical polarity proteins (AMOT, PARD6, and NF2) during the period of preimplantation embryogenesis. Cell–cell contact and cell polarity activate (phosphorylates) the core cascade components of the pathway (mammalian sterile twenty like 1 and 2 (MST1/2) and large tumor suppressor 1 and 2 (LATS1/2)), which in turn phosphorylate the downstream effectors of the pathway (YAP1/TAZ). The Hippo pathway remains inactive with YAP1 (Yes Associated protein 1) present inside the nucleus in the trophectoderm (TE) cells (polar blastomeres) of the mouse blastocyst. In the inner cell mass (ICM) cells (apolar blastomeres), the pathway is activated with p-YAP1 present in the cytoplasm. On the contrary, during bovine embryogenesis, p-YAP1 is exclusively present in the nucleus in both TE and ICM cells. Contrary to mouse embryos, transcription co activator with PDZ-binding motif (TAZ) (also known as WWTR1) is also predominantly present in the cytoplasm in all the blastomeres during bovine embryogenesis. This review outlines the major differences in the localization and function of Hippo signaling pathway components of murine and bovine preimplantation embryos, suggesting significant differences in the regulation of this pathway in between the two species. The variance observed in the Hippo signaling pathway between murine and bovine embryos confirms that both of these early embryonic models are quite distinct. Moreover, based on the similarity of the Hippo signaling pathway between bovine and human early embryo development, bovine embryos could be an alternate model for understanding the regulation of the Hippo signaling pathway in human embryos.

Differential regulation of Hippo signaling pathway components between 8‐cell and blastocyst stages of bovine preimplantation embryogenesis

“…Another possible explanation for the Hippo independent decrease in the gene expression of Yap1 can be due to the regulation of gene expression of Yap1 through other cell signaling pathways, such as the Mevalonate, RHO/ROCK (Rhoassociated kinase) and the Notch signaling pathways, as in the case of mouse (Kohri et al, 2020;Li et al, 2021;Teresa et al, 2014). | 157 (Bolmberg et al, 2008;Cockburn & Rossant, 2010;Sharma et al, 2021;Wei et al, 2017). Our morphological assessment studies suggest a significant decrease in the size of blastocoel cavities in the Cerivastatin treated blastocysts (0.5 µM), compared to the control (untreated) and vehicle treated blastocysts (*p < 0.001) (Supporting Information data, Figure S1a).…”

“…Success of in vitro fertilization (IVF) is primarily dependent on the formation of a healthy and viable blastocyst (Manzanares & Rodriguez, 2013; Watson, 1992; Watson, Kidder, et al, 1992). Four significant morphological changes precede blastocyst formation: fertilization, maternal to embryo transition (MET), compaction and cavitation (Graf et al, 2014; Meirelles et al, 2004; Sharma & Madan, 2020; Sharma et al, 2021). Fertilization refers to the syngamy of an oocyte with the sperm.…”

“…This event marks the stage of embryonic development where the further development of the embryo relies primarily on the transcription of its own genome (Meirelles et al, 2004; Memili & First, 2000; Misirlioglu et al, 2006; Sirard, 2010a). In addition to MET, establishment of cellular polarity and increased cell‐cell contact is also initiated at the 8‐cell stage (Sharma et al, 2021; Sirard, 2010a). MET is followed by the processes of compaction and cavitation.…”

“…The process of compaction occurs at the morula stage during bovine embryogenesis. During this process, the blastomeres lose their individual cell boundaries and compact together by increasing the intercellular contact, thereby leading to the formation of the morula (Bolmberg et al, 2008; Sharma & Madan, 2020; Sharma et al, 2021). The process of compaction is followed by cavitation.…”

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

“…The core Hippo pathway is evolutionary conserved and its homologues in mammals are involved in many cellular functions, such as proliferation and differentiation, as well as carcinogenesis. The main components are the serine-threonine kinases Ste-20-like kinases 1/2 (Mst1/2) and large tumor suppressor kinase 1/2 (Lats1/2) as well as the above-mentioned co-transcriptional activators, YAP and TAZ [13,[113][114][115][116].…”