Abstract
The segregation of trophectoderm (TE) and inner cell mass in early embryos is driven primarily by the transcription factor CDX2. The signals that trigger CDX2 activation are, however, less clear. In mouse embryos, the Hippo-YAP signaling pathway is important for the activation of CDX2 expression; it is less clear whether this relationship is conserved in other mammals. Lysophosphatidic acid (LPA) has been reported to increase YAP levels by inhibiting its degradation. In this study, we cultured bovine embryos in the presence of LPA and examined changes in gene and protein expression. LPA was found to accelerate the onset of blastocyst formation on days 5 and 6, without changing the TE/inner cell mass ratio. We further observed that the expression of TAZ and TEAD4 was up-regulated, and YAP was overexpressed, in LPA-treated day 6 embryos. However, LPA-induced up-regulation of CDX2 expression was only evident in day 8 embryos. Overall, our data suggest that the Hippo signaling pathway is involved in the initiation of bovine blastocyst formation, but does not affect the cell lineage constitution of blastocysts.
Highlights
During mammalian development, the first cell lineage specification is initiated at the compact morula stage, resulting in the formation of a blastocyst with an outer trophectoderm (TE) and an inner cell mass (ICM)
To examine how the Hippo pathway is involved in embryo development, bovine oocytes were fertilized in vitro and cultured to the day 8 blastocyst stage in the presence of 10−5 M Lysophosphatidic acid (LPA)
Our results demonstrate that LPA stimulation accelerates bovine blastocyst formation on days 5 and day 6 of in vitro culture, without changing the total cell number at day 6 or day 8
Summary
The first cell lineage specification is initiated at the compact morula stage, resulting in the formation of a blastocyst with an outer trophectoderm (TE) and an inner cell mass (ICM). The transcription factor CDX2 is crucial for proper TE specification [1], whereas OCT4, NANOG, and SOX2 are core regulators of ICM formation [2]. Emerging evidence has indicated that the Hippo-YAP signaling pathway plays an essential role in controlling the expression of the key transcription factors in first-lineage segregation (ICM and TE differentiation) during mouse preimplantation development [10,11,12,13]. In the cells on the outside of the morula, where the Hippo pathway is inactive, YAP/TAZ remain unphosphorylated and migrate to the nucleus to bind the transcriptional coactivator TEAD4 facilitating Cdx expression, and subsequently driving them to a TE fate [11,13,14]. There is no Cdx expression in these cells, driving them towards an ICM fate [16,17]
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