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Review
, 8 (2), 51-57
eCollection

The First Cell Fate Decision in Pre-Implantation Mouse Embryos

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Review

The First Cell Fate Decision in Pre-Implantation Mouse Embryos

Chunmeng Yao et al. Cell Regen (Lond).

Abstract

Fertilization happens when sperm and oocytes meet, which is a complicated process involving many important types of biological activation. Beginning in the 2-cell stage, an important event referred to as zygotic genome activation (ZGA) occurs, which governs the subsequent development of the embryo. In ZGA, multiple epigenetic modifications are involved and critical for pre-implantation development. These changes occur after ZGA, resulting in blastomeres segregate into two different lineages. Some blastomeres develop into the inner cell mass (ICM), and others develop into the trophectoderm (TE), which is considered the first cell fate decision. How this process is initiated and the exact molecular mechanisms involved are fascinating questions that remain to be answered. In this review, we introduce some possible developmental models of the first cell fate decision and discuss the signalling pathways and transcriptional networks regulating this process.

Keywords: Cell fate; Developmental models; Fertilization; Signalling pathways.

Figures

Fig. 1
Fig. 1
Fertilization and Zygotic Genome Activation (A) Dynamics of mRNA in the fertilized zygote. After fertilization, the maternal mRNA is gradually degraded until the 2-cell stage, when the mRNA of the zygote is activated (B) The first important event after fertilization is the development pattern of the embryo during the transition from maternal to zygotic expression beginning at the 2-cell stage; this process is termed the maternal–zygotic transition (MZT) or zygotic genome activation (ZGA). Thereafter, the compaction of the embryos and formation of the blastocoel indicate the initiation of the first cell fate decision.
Fig. 2
Fig. 2
Developmental Models of Cell Fate Decision and Spatial Patterning (A) “Inside-outside” model (“polarity” model): inner cells and outer cells of the morula take on different cell destinies during cell fate decisions (B) Spatial patterning in blastocyst formation: There are two cleavage orientations (meridional (M) and equatorial (E)) in 2-cell stage embryos. If the blastomeres divide in different orders, the contribution of the blastomeres is distinct.
Fig. 3
Fig. 3
Signalling and Transcriptional Regulation in ICM and TE Fates (A) Hippo pathway in the ICM and TE: Unphosphorylated Yap can be transported into the cell nucleus to bind with TEAD4 to activate the expression of Cdx2. Phosphorylated Yap in the ICM remains outside of the cell nucleus, resulting in the expression of Oct4. The Notch pathway in the TE: NICD and RBPJ form a complex that activates the expression of Cdx2. Angiomotin (Amot) is a key factor regulating the activation of Yap (B) Expression patterns of specific genes in ICM and TE fate.
Fig. 4
Fig. 4
Heterogeneous Expression in Early Blastomeres (A) Oct4 shows distinct kinetics in blastomeres at the 4-cell stage, resulting in cell fate segregation. Additionally, Sox2 shows different binding windows and also affects cell fate decision (B) Heterogeneous expression in the 4-cell stage: CARM1 is heterogeneously expressed in the 4-cell stage, resulting in the upregulation of Oct4 and Sox21 (target gene of Sox2) and decision of the ICM. LincGET is heterogeneously expressed in the blastomeres of 2-cell embryos and binds to CARM1 and affects ICM formation. In addition, Neat1 combines with Carm1 to form a paraspeckle to regulate ICM/TE cell fates.

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