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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

Oct4 expression during the mouse life cycle. Cells and tissues expressing Oct4 are marked in green. Oct4 is expressed in mouse oocytes as a maternal transcript and protein. Zygotic Oct4 expression is activated prior to the 8-cell stage and is abundant and uniform in all cells of the embryo throughout the morula stage. However, as the outer cells of the embryo differentiate into the TE, Oct4 expression is restricted to cells of the ICM in the blastocyst. After implantation, Oct4 expression is maintained in the epiblast. Finally, Oct4 expression becomes restricted to primordial germ cells (PGCs), which are first specified in the extraembryonic mesoderm at the base of the allantoic bud during gastrulation. PGCs give rise to gametes, which following fertilization will develop into a new organism of next generation. Oct4 expression is based on data previously reported by several studies [6, 7, 9–11].
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Fig1: Oct4 expression during the mouse life cycle. Cells and tissues expressing Oct4 are marked in green. Oct4 is expressed in mouse oocytes as a maternal transcript and protein. Zygotic Oct4 expression is activated prior to the 8-cell stage and is abundant and uniform in all cells of the embryo throughout the morula stage. However, as the outer cells of the embryo differentiate into the TE, Oct4 expression is restricted to cells of the ICM in the blastocyst. After implantation, Oct4 expression is maintained in the epiblast. Finally, Oct4 expression becomes restricted to primordial germ cells (PGCs), which are first specified in the extraembryonic mesoderm at the base of the allantoic bud during gastrulation. PGCs give rise to gametes, which following fertilization will develop into a new organism of next generation. Oct4 expression is based on data previously reported by several studies [6, 7, 9–11].

Mentions: Life is like a journey of torch relay. From generation to generation, our bodies vanish at the end of our lives, but the germ cells are passed on to the next generation, ensuring the continuity and prosperity of our species. In comparison with the somatic cells, these germ cells possess many unique properties, of which the expression of Oct4 is the most important as it is required for the survival of primordial germ cells (PGCs) [1, 2]. Oct4 is also expressed specifically in the inner cell mass (ICM) and embryonic stem cells (ESCs), the cells derived from the ICM [3]. Interestingly, Oct4 is expressed in mouse oocytes as a maternal transcript and protein [1, 4–6]. As is typical for most maternal mRNAs, levels of Oct4 mRNA drop dramatically after fertilization [6]. Zygotic Oct4 expression is activated prior to the 8-cell stage, with a significant increase in both mRNA and protein levels [4, 6]. Oct4 expression is abundant and uniform in all cells of the embryo throughout the morula stage. However, as the outer cells of the embryo differentiate into the trophectoderm (TE), Oct4 expression becomes downregulated and restricted to cells of the ICM in the blastocyst [5, 7, 8]. When cells of the primitive endoderm differentiate and migrate away from the ectoderm, their Oct4 protein levels transiently increase [4]. Oct4 expression then becomes downregulated in the primitive endoderm and maintained in the epiblast, concurrently with embryo implantation and gastrulation. Oct4 expression finally becomes restricted to PGCs [9], which are first specified in the extraembryonic mesoderm at the base of the allantoic bud during gastrulation [9]. PGCs give rise to gametes, which can be fertilized to develop into a new fully functional organism of the next generation and complete one cycle of life (Figure 1).Figure 1


Role of Oct4 in the early embryo development.

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

Oct4 expression during the mouse life cycle. Cells and tissues expressing Oct4 are marked in green. Oct4 is expressed in mouse oocytes as a maternal transcript and protein. Zygotic Oct4 expression is activated prior to the 8-cell stage and is abundant and uniform in all cells of the embryo throughout the morula stage. However, as the outer cells of the embryo differentiate into the TE, Oct4 expression is restricted to cells of the ICM in the blastocyst. After implantation, Oct4 expression is maintained in the epiblast. Finally, Oct4 expression becomes restricted to primordial germ cells (PGCs), which are first specified in the extraembryonic mesoderm at the base of the allantoic bud during gastrulation. PGCs give rise to gametes, which following fertilization will develop into a new organism of next generation. Oct4 expression is based on data previously reported by several studies [6, 7, 9–11].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Oct4 expression during the mouse life cycle. Cells and tissues expressing Oct4 are marked in green. Oct4 is expressed in mouse oocytes as a maternal transcript and protein. Zygotic Oct4 expression is activated prior to the 8-cell stage and is abundant and uniform in all cells of the embryo throughout the morula stage. However, as the outer cells of the embryo differentiate into the TE, Oct4 expression is restricted to cells of the ICM in the blastocyst. After implantation, Oct4 expression is maintained in the epiblast. Finally, Oct4 expression becomes restricted to primordial germ cells (PGCs), which are first specified in the extraembryonic mesoderm at the base of the allantoic bud during gastrulation. PGCs give rise to gametes, which following fertilization will develop into a new organism of next generation. Oct4 expression is based on data previously reported by several studies [6, 7, 9–11].
Mentions: Life is like a journey of torch relay. From generation to generation, our bodies vanish at the end of our lives, but the germ cells are passed on to the next generation, ensuring the continuity and prosperity of our species. In comparison with the somatic cells, these germ cells possess many unique properties, of which the expression of Oct4 is the most important as it is required for the survival of primordial germ cells (PGCs) [1, 2]. Oct4 is also expressed specifically in the inner cell mass (ICM) and embryonic stem cells (ESCs), the cells derived from the ICM [3]. Interestingly, Oct4 is expressed in mouse oocytes as a maternal transcript and protein [1, 4–6]. As is typical for most maternal mRNAs, levels of Oct4 mRNA drop dramatically after fertilization [6]. Zygotic Oct4 expression is activated prior to the 8-cell stage, with a significant increase in both mRNA and protein levels [4, 6]. Oct4 expression is abundant and uniform in all cells of the embryo throughout the morula stage. However, as the outer cells of the embryo differentiate into the trophectoderm (TE), Oct4 expression becomes downregulated and restricted to cells of the ICM in the blastocyst [5, 7, 8]. When cells of the primitive endoderm differentiate and migrate away from the ectoderm, their Oct4 protein levels transiently increase [4]. Oct4 expression then becomes downregulated in the primitive endoderm and maintained in the epiblast, concurrently with embryo implantation and gastrulation. Oct4 expression finally becomes restricted to PGCs [9], which are first specified in the extraembryonic mesoderm at the base of the allantoic bud during gastrulation [9]. PGCs give rise to gametes, which can be fertilized to develop into a new fully functional organism of the next generation and complete one cycle of life (Figure 1).Figure 1

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