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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

Schematic representation of the protein domains of the mouse Oct4 isoforms and the corresponding exons. Exon1B of Oct4B is in the intron 1–2 region of the Oct4 gene. Modified from Guo et al. 2012 [81].
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Fig3: Schematic representation of the protein domains of the mouse Oct4 isoforms and the corresponding exons. Exon1B of Oct4B is in the intron 1–2 region of the Oct4 gene. Modified from Guo et al. 2012 [81].

Mentions: After the finding that truncated isoforms of OCT4 are transcribed from the POU5F1 gene in human [76] and mouse [77], the originally described OCT4 is designated as OCT4A and the newly found truncated isoforms are variants of an OCT4 version named OCT4B [78]. OCT4B mRNAs encode proteins that have identical POU DNA-binding domains and C-domains but differ in their N-domains (Figure 3). Continued expression of Oct4B after the original Oct4 promoter was removed indicates that Oct4B transcription is regulated by an alternative promoter in the first intron [37], as presumed by an earlier study [79]. Other isoforms of Oct4B could be produced by alternative splicing or alternative translation initiation [80, 81]. ESC-based complementation assays using ZHBTc4 ESCs, which has endogenous Oct4 inactivated by gene targeting and harbors a tetracycline-repressible Oct4 transgene to support ESC self-renewal [44], showed that OCT4B cannot rescue the self-renewal ability of ZHBTc4 ESCs in the presence of doxycycline, unlike OCT4A. Electrophonetic mobility shift assay showed that OCT4B does not bind to a probe carrying the OCT4 consensus binding sequence due to the repressive effect of the OCT4B N-domain. Furthermore, overexpression of OCT4B does not activate transcription from OCT4-dependent promoters [78]. However, Oct4B is involved in stress response [82] and acts as an antiapoptotic factor in cancer cells [83].Figure 3


Role of Oct4 in the early embryo development.

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

Schematic representation of the protein domains of the mouse Oct4 isoforms and the corresponding exons. Exon1B of Oct4B is in the intron 1–2 region of the Oct4 gene. Modified from Guo et al. 2012 [81].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Schematic representation of the protein domains of the mouse Oct4 isoforms and the corresponding exons. Exon1B of Oct4B is in the intron 1–2 region of the Oct4 gene. Modified from Guo et al. 2012 [81].
Mentions: After the finding that truncated isoforms of OCT4 are transcribed from the POU5F1 gene in human [76] and mouse [77], the originally described OCT4 is designated as OCT4A and the newly found truncated isoforms are variants of an OCT4 version named OCT4B [78]. OCT4B mRNAs encode proteins that have identical POU DNA-binding domains and C-domains but differ in their N-domains (Figure 3). Continued expression of Oct4B after the original Oct4 promoter was removed indicates that Oct4B transcription is regulated by an alternative promoter in the first intron [37], as presumed by an earlier study [79]. Other isoforms of Oct4B could be produced by alternative splicing or alternative translation initiation [80, 81]. ESC-based complementation assays using ZHBTc4 ESCs, which has endogenous Oct4 inactivated by gene targeting and harbors a tetracycline-repressible Oct4 transgene to support ESC self-renewal [44], showed that OCT4B cannot rescue the self-renewal ability of ZHBTc4 ESCs in the presence of doxycycline, unlike OCT4A. Electrophonetic mobility shift assay showed that OCT4B does not bind to a probe carrying the OCT4 consensus binding sequence due to the repressive effect of the OCT4B N-domain. Furthermore, overexpression of OCT4B does not activate transcription from OCT4-dependent promoters [78]. However, Oct4B is involved in stress response [82] and acts as an antiapoptotic factor in cancer cells [83].Figure 3

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