WNT signalling supported by MEK/ERK inhibition is essential to maintain pluripotency in bovine preimplantation embryo

Warzych, Ewelina; Pawlak, Piotr; Lechniak, D.; Madeja, Zofia E.

doi:10.1016/j.ydbio.2020.04.004

Cited by 12 publications

(39 citation statements)

References 99 publications

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“…We further investigated the second lineage segregation in bovine blastocysts by inhibiting the MEK pathway with PD032. In line with previous reports, MEK-inhibition did not completely ablate GATA6 positive cells [ 18 , 20 ], and also SOX17 was still expressed in the ICM. Canizo, et al [ 22 ] found a dosage-dependent effect of PD032 with the concentration also applied in this study abolishing all SOX17.…”

Section: Discussionsupporting

confidence: 92%

“…In bovine embryos, MEK inhibition increases NANOG expression and reduces HB markers, but HB marker expression is still present. In human embryos, MEK inhibition has no effect, suggesting that bovine and human HB formation is partly or completely independent of this pathway, and that these species regulate the second lineage differentiation differently [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, a dosage-dependent effect of the MEK-inhibitory compound PD0325901 (PD032) was found in bovine embryos. A concentration of 2.5 µM eliminated expression of the later HB-marker SOX17 completely [ 22 ], while previous studies observed maintenance of the early marker GATA6 at concentrations of 0.5 and 1 µM [ 18 , 20 ], challenging the hypothesis of a partly MEK-independent HB formation in bovine.…”

Section: Introductionmentioning

confidence: 99%

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Hypoblast Formation in Bovine Embryos Does Not Depend on NANOG

Springer

Zakhartchenko

Wolf

et al. 2021

Cells

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The role of the pluripotency factor NANOG during the second embryonic lineage differentiation has been studied extensively in mouse, although species-specific differences exist. To elucidate the role of NANOG in an alternative model organism, we knocked out NANOG in fibroblast cells and produced bovine NANOG-knockout (KO) embryos via somatic cell nuclear transfer (SCNT). At day 8, NANOG-KO blastocysts showed a decreased total cell number when compared to controls from SCNT (NT Ctrl). The pluripotency factors OCT4 and SOX2 as well as the hypoblast (HB) marker GATA6 were co-expressed in all cells of the inner cell mass (ICM) and, in contrast to mouse Nanog-KO, expression of the late HB marker SOX17 was still present. We blocked the MEK-pathway with a MEK 1/2 inhibitor, and control embryos showed an increase in NANOG positive cells, but SOX17 expressing HB precursor cells were still present. NANOG-KO together with MEK-inhibition was lethal before blastocyst stage, similarly to findings in mouse. Supplementation of exogenous FGF4 to NANOG-KO embryos did not change SOX17 expression in the ICM, unlike mouse Nanog-KO embryos, where missing SOX17 expression was completely rescued by FGF4. We conclude that NANOG mediated FGF/MEK signaling is not required for HB formation in the bovine embryo and that another—so far unknown—pathway regulates HB differentiation.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypoblast Formation in Bovine Embryos Does Not Depend on NANOG

Springer

Zakhartchenko

Wolf

et al. 2021

Cells

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“…Inhibition of MAPK in N2B27 medium showed a dose-dependent response, where increasing the concentration of the inhibitor eventually completely ablated SOX17 expression [ 158 ]. When bovine embryos are cultured in the 2i system, which activates the WNT pathway and inhibits MAPK, NANOG expression is increased and GATA6 still present [ 159 ].…”

Section: New Insights Into Preimplantation Development From Alternative Model Organismsmentioning

confidence: 99%

A New Toolbox in Experimental Embryology—Alternative Model Organisms for Studying Preimplantation Development

Springer

Wolf

Simmet

2021

JDB

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Preimplantation development is well conserved across mammalian species, but major differences in developmental kinetics, regulation of early lineage differentiation and implantation require studies in different model organisms, especially to better understand human development. Large domestic species, such as cattle and pig, resemble human development in many different aspects, i.e., the timing of zygotic genome activation, mechanisms of early lineage differentiations and the period until blastocyst formation. In this article, we give an overview of different assisted reproductive technologies, which are well established in cattle and pig and make them easily accessible to study early embryonic development. We outline the available technologies to create genetically modified models and to modulate lineage differentiation as well as recent methodological developments in genome sequencing and imaging, which form an immense toolbox for research. Finally, we compare the most recent findings in regulation of the first lineage differentiations across species and show how alternative models enhance our understanding of preimplantation development.

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“…In bovines, many genes show differences in expression between ICM and TE that differs from that observed in mouse or human species [4]. The lineage specification in cattle seems to be directed by a different set of regulatory factors [5]. Moreover, the precise molecular interactions governing ICM/TE specification in this species has not been totally clarified yet [6].…”

Section: Introductionmentioning

confidence: 95%

Pluripotent Core in Bovine Embryos: A Review

Águila¹,

Osycka‐Salut²,

Treulén³

et al. 2022

Preprint

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Early development in mammals is characterized by the ability of each cell to produce a complete organism plus the extraembryonic, or placental, cells, defined as pluripotency. During subsequent development, pluripotency is lost, and cells begin to differentiate to a particular cell fate. This review summarizes the current knowledge of pluripotency features of bovine embryos cultured in vitro, focusing on the core of pluripotency genes (OCT4, NANOG, SOX2, and CDX2), and main chemical strategies for controlling pluripotent networks during early development. Finally, we will discuss the applicability of manipulating pluripotency during morula to blastocyst transition in cattle species.

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WNT signalling supported by MEK/ERK inhibition is essential to maintain pluripotency in bovine preimplantation embryo

Cited by 12 publications

References 99 publications

Hypoblast Formation in Bovine Embryos Does Not Depend on NANOG

Hypoblast Formation in Bovine Embryos Does Not Depend on NANOG

A New Toolbox in Experimental Embryology—Alternative Model Organisms for Studying Preimplantation Development

Pluripotent Core in Bovine Embryos: A Review

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