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Role of Oct4 in the early embryo development.

Wu G, Schöler HR - Cell Regen (Lond) (2014)

Bottom Line: Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development.These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency.This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.

ABSTRACT
Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast. Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development. However, the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4-depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect. These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency. This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

No MeSH data available.


Related in: MedlinePlus

Development of maternal Oct4–depleted embryos. Totipotency in maternal Oct4–depleted embryos can be established in the absence of Oct4, and these embryos can maintain pluripotency and complete full-term development, supported by the zygotic activation of the paternal allele Oct4 gene at the late 4-cell stage. The lower panel shows that in the absence of both maternal and zygotic Oct4 expression, the Nanog-positive ICM and Cdx2-positive TE lineages are still established. However, this ICM cannot maintain pluripotency and complete the second lineage separation, and it fails to further develop at around the time of implantation. dpc: days post coitum; dpp: days post partum; ZGA: zygotic genome activation.
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Fig4: Development of maternal Oct4–depleted embryos. Totipotency in maternal Oct4–depleted embryos can be established in the absence of Oct4, and these embryos can maintain pluripotency and complete full-term development, supported by the zygotic activation of the paternal allele Oct4 gene at the late 4-cell stage. The lower panel shows that in the absence of both maternal and zygotic Oct4 expression, the Nanog-positive ICM and Cdx2-positive TE lineages are still established. However, this ICM cannot maintain pluripotency and complete the second lineage separation, and it fails to further develop at around the time of implantation. dpc: days post coitum; dpp: days post partum; ZGA: zygotic genome activation.

Mentions: As summarized in Figure 4, new pieces of evidence clearly indicate that Oct4 is not the master regulator responsible for initiating totipotency-pluripotency in oocytes, and that maternal and zygotic Oct4– blastocysts maintain the ability to activate Nanog and Oct4-GFP expression, indicating that unknown pathways other than the Oct4-centered pluripotency-regulating network are active in embryos and function upstream of Oct4 in driving pluripotency. However, to date no factors have proven to be essential for Oct4 activation in the preimplantation embryos. Further studies are required to elucidate how oocytes activate the pluripotent genes Oct4 and Nanog on top of the Oct4/Sox2 autoregulatory loop in an effort to understand the establishment of totipotency in zygotes and in transplanted somatic cells.Figure 4


Role of Oct4 in the early embryo development.

Wu G, Schöler HR - Cell Regen (Lond) (2014)

Development of maternal Oct4–depleted embryos. Totipotency in maternal Oct4–depleted embryos can be established in the absence of Oct4, and these embryos can maintain pluripotency and complete full-term development, supported by the zygotic activation of the paternal allele Oct4 gene at the late 4-cell stage. The lower panel shows that in the absence of both maternal and zygotic Oct4 expression, the Nanog-positive ICM and Cdx2-positive TE lineages are still established. However, this ICM cannot maintain pluripotency and complete the second lineage separation, and it fails to further develop at around the time of implantation. dpc: days post coitum; dpp: days post partum; ZGA: zygotic genome activation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230828&req=5

Fig4: Development of maternal Oct4–depleted embryos. Totipotency in maternal Oct4–depleted embryos can be established in the absence of Oct4, and these embryos can maintain pluripotency and complete full-term development, supported by the zygotic activation of the paternal allele Oct4 gene at the late 4-cell stage. The lower panel shows that in the absence of both maternal and zygotic Oct4 expression, the Nanog-positive ICM and Cdx2-positive TE lineages are still established. However, this ICM cannot maintain pluripotency and complete the second lineage separation, and it fails to further develop at around the time of implantation. dpc: days post coitum; dpp: days post partum; ZGA: zygotic genome activation.
Mentions: As summarized in Figure 4, new pieces of evidence clearly indicate that Oct4 is not the master regulator responsible for initiating totipotency-pluripotency in oocytes, and that maternal and zygotic Oct4– blastocysts maintain the ability to activate Nanog and Oct4-GFP expression, indicating that unknown pathways other than the Oct4-centered pluripotency-regulating network are active in embryos and function upstream of Oct4 in driving pluripotency. However, to date no factors have proven to be essential for Oct4 activation in the preimplantation embryos. Further studies are required to elucidate how oocytes activate the pluripotent genes Oct4 and Nanog on top of the Oct4/Sox2 autoregulatory loop in an effort to understand the establishment of totipotency in zygotes and in transplanted somatic cells.Figure 4

Bottom Line: Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development.These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency.This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.

ABSTRACT
Oct4 is a key component of the pluripotency regulatory network, and its reciprocal interaction with Cdx2 has been shown to be a determinant of either the self-renewal of embryonic stem cells (ESCs) or their differentiation into trophoblast. Oct4 of maternal origin is postulated to play critical role in defining totipotency and inducing pluripotency during embryonic development. However, the genetic elimination of maternal Oct4 using a Cre-lox approach in mouse revealed that the establishment of totipotency in maternal Oct4-depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect. These results indicate that Oct4 is not essential for the initiation of pluripotency, in contrast to its critical role in maintaining pluripotency. This conclusion is further supported by the formation of Oct4-GFP- and Nanog- expressing inner cell masses (ICMs) in embryos with complete inactivation of both maternal and zygotic Oct4 expression and the reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

No MeSH data available.


Related in: MedlinePlus