GATA6 Levels Modulate Primitive Endoderm Cell Fate Choice and Timing in the Mouse Blastocyst

Schrode, Nadine; Saiz, Néstor; Talia, Stefano Di; Hadjantonakis, Anna-Katerina

doi:10.1016/j.devcel.2014.04.011

Cited by 210 publications

(307 citation statements)

References 48 publications

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“…Jens-Erik Dietrich et al Venus trap in the mouse embryo EMBO reports may be largely driven by asymmetric division, while that for the ICM marker may not be following the same mechanism. The mechanism regulating the ICM marker expression remains elusive, and the initiation of expression appears stochastic in the morula and early blastocyst stages without obvious correlation with position and the future lineage [4,8]. This finding is in line with our recent single-cell gene expression profiling study demonstrating genome-wide stochastic gene expression in the inner cells of the 32-cell stage blastocyst [7].…”

Section: à5supporting

confidence: 79%

Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages

et al. 2015

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Mammalian development begins with the segregation of embryonic and extra-embryonic lineages in the blastocyst. Recent studies revealed cell-to-cell gene expression heterogeneity and dynamic cell rearrangements during mouse blastocyst formation. Thus, mechanistic understanding of lineage specification requires quantitative description of gene expression dynamics at a singlecell resolution in living embryos. However, only a few fluorescent gene expression reporter mice are available and quantitative live image analysis is limited so far. Here, we carried out a fluorescence gene-trap screen and established reporter mice expressing Venus specifically in the first lineages. Lineage tracking, quantitative gene expression and cell position analyses allowed us to build a comprehensive lineage map of mouse pre-implantation development. Our systematic analysis revealed that, contrary to the available models, the timing and mechanism of lineage specification may be distinct between the trophectoderm and the inner cell mass. While expression of our trophectoderm-specific lineage marker is upregulated in outside cells upon asymmetric divisions at 8-and 16-cell stages, the inside-specific upregulation of the inner-cell-mass marker only becomes evident at the 64-cell stage. This study thus provides a framework toward systems-level understanding of embryogenesis marked by high dynamicity and stochastic variability.

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Section: à5supporting

confidence: 79%

Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages

et al. 2015

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“…Nanog-deficient mouse embryos are arrested during post-implantation development because of the widespread expression of Gata6 in the EPI (Mitsui et al 2003, Frankenberg et al 2011. By contrast, Gata6-deficient mouse embryos are arrested during postimplantation development because of the widespread expression of Nanog in the PE (Morris et al 2010, Schrode et al 2014. In the present study, we showed that Smyd3 knockdown led to the suppression of the embryonic transcription of Oct4 during the four-cell stage.…”

Section: Discussionmentioning

confidence: 47%

“…In mouse preimplantation embryos, Oct4, Nanog, and Sox2 are required for the maintenance of ICM pluripotency (Nichols et al 1998, Avilion et al 2003, Mitsui et al 2003. Additionally, Nanog is known to negatively interact with Gata6, and both genes are known to be key regulators in the establishment of EPI and PE fates respectively (Morris et al 2010, Frankenberg et al 2011, Kang et al 2013, Schrode et al 2014. Nanog-deficient mouse embryos are arrested during post-implantation development because of the widespread expression of Gata6 in the EPI (Mitsui et al 2003, Frankenberg et al 2011.…”

Section: Discussionmentioning

confidence: 99%

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

Suzuki¹,

Nozawa²,

Tsukamoto³

et al. 2015

Reproduction

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SET and MYND domain-containing protein 3 (Smyd3) is a histone H3 lysine 4 (H3K4) di-and tri-methyltransferase that forms a transcriptional complex with RNA polymerase II and activates the transcription of oncogenes and cell cycle genes in human cancer cells. However, the study of Smyd3 in mammalian early embryonic development has not yet been addressed. In the present study, we investigated the expression pattern of Smyd3 in mouse preimplantation embryos and the effects of RNA interference (RNAi)-mediated Smyd3 repression on the development of mouse embryos. We showed that Smyd3 mRNA levels increased after the two-cell stage, peaked at the four-cell stage, and gradually decreased thereafter. Moreover, in two-cell to eight-cell embryos, SMYD3 staining was more intense in the nuclei than it was in the cytoplasm. In Smyd3-knockdown embryos, the percentage of inner cell mass (ICM)-derived colony formation and trophectoderm (TE)-derived cell attachment were significantly decreased, which resulted in a reduction in the number of viable offspring. Furthermore, the expression of Oct4 and Cdx2 during mid-preimplantation gene activation was significantly decreased in Smyd3-knockdown embryos. In addition, the transcription levels of ICM and epiblast markers, such as Oct4, Nanog, and Sox2, the transcription levels of primitive endoderm markers, such as Gata6, and the transcription levels of TE markers, such as Cdx2 and Eomes, were significantly decreased in Smyd3-knockdown blastocysts. These findings indicate that SMYD3 plays an important role in early embryonic lineage commitment and peri-implantation development through the activation of lineage-specific genes.Reproduction (2015) 150 21-30

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“…On the other hand, the expression levels of the neuroectoderm marker ASCL1 (a transcription factor also known as MASH1) [22,23] were significantly upregulated ( Figure 2C, P < 0.05). The expression levels of the primitive endoderm marker GATA6 [24,25], encoding a transcription factor, were also upregulated, and those of the trophectoderm marker CDX2 [26,27], also encoding a transcription factor, were transiently upregulated during the progression of differentiation. The expression of endogenous TPRX1 mRNA was almost undetectable, whereas exogenous TPRX1 mRNA in NT2/D1 cells transfected with a TPRX1 expression vector (+FLAG/TPRX1) was clearly detected ( Figure 2D).…”

Section: Resultsmentioning

confidence: 91%

Exogenous TPRX1 homeoprotein modulates the gene expression of lineage-specific transcription factors in human embryonal carcinoma cells

Mori

Sakuraoka

Suzuki

et al. 2018

Biotechnology & Biotechnological Equipment

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We reported previously that EGAM1 homeoproteins (EGAM1 and EGAM1N), transcribed from the Crxos gene as splicing variants, are expressed in preimplantation mouse embryos and mouse embryonic stem (ES) cells. Exogenous expression of these proteins affects the maintenance of an undifferentiated state and the progression of differentiation in mouse ES cells. Human tetrapeptide-repeat homeobox 1 (TPRX1), a member of the eutherian totipotent cell homeobox (ETCHbox) genes, is an ortholog of Crxos. However, the roles of TPRX1 in the differentiation of human pluripotent cells are still unknown. Because the TPRX1 transcripts were undetectable in an undifferentiated state and during the progression of differentiation in wild-type human embryonal carcinoma NT2/D1 cells, it would be advantageous to clarify the relationship between the exogenous expression of TPRX1 and the induction of genes encoding lineage-specific transcription factors in pluripotent cells. The expression of GATA6 and FOXA2, crucial transcription factors for the formation of the primitive endoderm, was upregulated, whereas that of CDX2, a crucial transcription factor for the formation of the trophectoderm, was downregulated by enforced expression of TPRX1. Overall, we suggest that TPRX1 is capable of modulating the expression of lineage-specific transcription factors in pluripotent cells derived from humans.

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GATA6 Levels Modulate Primitive Endoderm Cell Fate Choice and Timing in the Mouse Blastocyst

Cited by 210 publications

References 48 publications

Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages

Venus trap in the mouse embryo reveals distinct molecular dynamics underlying specification of first embryonic lineages

Histone methyltransferase Smyd3 regulates early embryonic lineage commitment in mice

Exogenous TPRX1 homeoprotein modulates the gene expression of lineage-specific transcription factors in human embryonal carcinoma cells

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