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

Genes (Basel). 2021 Feb 16;12(2):281. doi: 10.3390/genes12020281.

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.

Keywords: Hippo; LATS1/2 (Large Tumor Suppressor 1 and 2); MS1/2 (Mammalian Sterile Twenty Like 1 and 2); TAZ (Transcriptional co activator with PDZ-binding motif); TEAD4 (TEA domain transcription factor 4); YAP1 (Yes Associated Protein 1); blastocyst; p-YAP1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Cattle
  • Cell Polarity / genetics
  • Embryonic Development / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Hippo Signaling Pathway
  • Humans
  • Mice
  • Protein Serine-Threonine Kinases / genetics*
  • Signal Transduction / genetics
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Wwtr1 protein, mouse
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Lats1 protein, mouse
  • Protein Serine-Threonine Kinases