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.
Highlights
Preimplantation Embryonic Development until Blastocyst FormationThe preimplantation period of development is broadly classified as the time from fertilization to mammalian blastocyst formation
During mouse blastocyst formation, LATS mediated Hippo signaling is inactive in the outer cells (TE), whereas this cell signaling is active in inner cells (ICM) owing to phosphorylation of LATS (p-LATS), thereby leading to activation of the Hippo signaling pathway [36,52] (Figure 1)
The localization of Hippo signaling pathway components is significantly different between bovine and mouse embryogenesis, suggesting the Hippo signaling pathway is differentially regulated in bovine embryos as compared with mouse embryos [33,51,59,65]
Summary
The preimplantation period of development is broadly classified as the time from fertilization to mammalian blastocyst formation. Polar cells form the outer trophectoderm (TE), whereas the apolar cells become the inner cell mass (ICM) [23] Each of these three classic models and there combinations have been used to interpret the results related to the process of cell fate specification during blastocyst formation. Another theory known as the “self-organization theory” postulated by Nodal and Lefty has been shown to explain the new observations made about the process of lineage segregation during mouse blastocyst formation According to this theory, known as the “reaction-diffusion pattern mechanism”, the process of cell fate specification in not just dependent upon one single factor, but is dependent on multiple variables such as cell division pattern, cell shape, cell adhesion, and lineage specific gene expression [21,26,27]. Numerous cell signaling pathways, such as the Wnt, Notch, MAPK, and Hippo signaling pathway, play a significant role in cell fate specification and are involved in the formation of blastocyst [8,28,29,30,31]
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