Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo

Płusa, Berenika; Frankenberg, Stephen; Chalmers, Andrew D.; Hadjantonakis, Anna-Katerina; Moore, Catherine; Papalopulu, Nancy; Papaioannou, Virginia E.; Glover, David M.; Zernicka‐Goetz, Magdalena

doi:10.1242/jcs.01666

Cited by 243 publications

(262 citation statements)

References 42 publications

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“…Of interest, overexpression of either dominant-negative PKC , an aPKC, or to a lesser extent, RNA interference-mediated knockdown of ParD3 at the four-cell stage causes injected cells to preferentially occupy the ICM position at the blastocyst stage (Plusa et al, 2005b). Although it is not clear whether injected cells adopted an ICM fate, these observations support the notion that a functional apical domain is essential for polarity, outside cell formation, and probably TE fate (Fig.…”

Section: Molecular Regulation Of Te Vs Icm Fate Choicementioning

confidence: 55%

Cell and molecular regulation of the mouse blastocyst

Yamanaka

Ralston

Stephenson

et al. 2006

Developmental Dynamics

264

221

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Animals use diverse strategies to specify tissue lineages during development. A common strategy is to partition maternally supplied and localized lineage determinants into progenitor cells. The mouse embryo appears to use a different, more regulative strategy to specify the first three lineages: the epiblast (EPI: future embryo), the trophectoderm (TE: future placenta), and the primitive endoderm (PE: future yolk sac). These lineages are specified during two successive differentiation steps leading to formation of the blastocyst. Here, we review classic and contemporary models of early lineage specification in the mouse, and describe recent efforts to understand the molecular regulation of these events. We describe evidence that trophectoderm differentiation bears resemblance to the process of epithelialization and describe the importance of apical/basal protein complexes in regulating this process. Next, we present a revised model of PE specification, and describe evidence that PE cells in the inner cell mass sort out to occupy their ultimate position on the surface of the EPI. Finally, we describe factors that reinforce these lineages and three distinct stem cell types that can be isolated from them. Together, these mechanisms guide the differentiation of the first lineages of the mouse and thereby set up tissues that will be important for the first steps of embryonic body patterning. Developmental Dynamics 235:2301-2314, 2006.

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Section: Molecular Regulation Of Te Vs Icm Fate Choicementioning

confidence: 55%

Cell and molecular regulation of the mouse blastocyst

Yamanaka

Ralston

Stephenson

et al. 2006

Developmental Dynamics

264

221

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“…For this, the post-transcriptional gene silencing (PTGS) by doublestranded RNA (dsRNA) or RNA interference (RNAi) has emerged as a new tool for studying gene function in an increasing number of organisms (Fire 1999). Following its application in Caenorhabditis elegance (Fire et al 1998), the RNAi approach by introduction of dsRNA has been used in various mammalian species such as human (Brusselmans et al 2005, Cheng et al 2005, Hyslop et al 2005, mouse (Svoboda et al 2000, Wianny & ZernickaGoetz 2000, Grabarek et al 2002, Stein et al 2003, Alizadeh et al 2005, Gui & Joyce 2005, Plusa et al 2005) and porcine (Cabot & Prather 2003). Most recently, the work by our group (Nganvongpanit et al 2006) and others (Paradis et al 2005) have used the RNAi approach to suppress transcripts in bovine embryos and oocytes respectively.…”

Section: Introductionmentioning

confidence: 99%

“…Most recently, the work by our group (Nganvongpanit et al 2006) and others (Paradis et al 2005) have used the RNAi approach to suppress transcripts in bovine embryos and oocytes respectively. Recently, microinjection of dsRNA which interferes with genes that regulate cell polarity (Par3 and aPKC) in randomly selected blastomeres of cleavage-stage mouse embryos has enabled direction of defined cells to new positions and redirection of their fate in the preimplantation embryos (Plusa et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Selective degradation of maternal and embryonic transcripts in in vitro produced bovine oocytes and embryos using sequence specific double-stranded RNA

Nganvongpanit

Müller²,

Rings³

et al. 2006

Reproduction

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RNA interference (RNAi) has been used for selective degradation of an mRNA transcript or inhibiting its translation to a functional protein in various species. Here, we applied the RNAi approach to suppress the expression of the maternal transcript C-mos and embryonic transcripts Oct-4 in bovine oocytes and embryos respectively, using microinjection of sequence-specific double-stranded RNA (dsRNA). For this, 435 bp C-mos and 341 bp Oct-4 dsRNA were synthesized and microinjected into the cytoplasm of immature oocytes and zygotes respectively. In experiment 1, immature oocytes were categorized into three groups: those injected with C-mos dsRNA, RNase-free water and uninjected controls. In experiment 2, in vitro produced zygotes were categorized into three groups: those injected with Oct-4 dsRNA, RNase-free water and uninjected controls. The developmental phenotypes, the level of mRNA and protein expression were investigated after treatment in both experiments. Microinjection of C-mos dsRNA has resulted in 70% reduction of C-mos transcript after maturation compared to the water-injected and uninjected controls (P!0.01). Microinjection of zygotes with Oct-4 dsRNA has resulted in 72% reduction in transcript abundance at the blastocyst stage compared to the uninjected control zygotes (P!0.01). Moreover, a significant reduction in the number of inner cell mass (ICM) cells was observed in Oct-4 dsRNA-injected embryos compared to the other groups. From oocytes injected with C-mos dsRNA, 60% showed the extrusion of the first polar body compared to 50% in water-injected and 44% in uninjected controls. Moreover, only oocytes injected with C-mos dsRNA showed spontaneous activation. In conclusion, our results demonstrated that sequence-specific dsRNA can be used to knockdown maternal or embryonic transcripts in bovine embryogenesis.

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“…It remains an open question when and how the first cell fate decision is made. Cell fate-associated inter-blastomere differences in transcript and protein concentrations were reported as early as the 8-16 cell stage (Avilion et al 2003;Plusa et al 2005a;Zhang et al 2006;Yagi et al 2007;Jedrusik et al 2008;Nishioka et al 2008;Guo et al 2010). However, it is not clear whether these are the earliest differences.…”

mentioning

confidence: 99%

Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing

2014

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It remains an open question when and how the first cell fate decision is made in mammals. Using deep single-cell RNA-seq of matched sister blastomeres, we report highly reproducible inter-blastomere differences among 10 2-cell and five 4-cell mouse embryos. Inter-blastomere gene expression differences dominated between-embryo differences and noise, and were sufficient to cluster sister blastomeres into distinct groups. Dozens of protein-coding genes exhibited reproducible bimodal expression in sister blastomeres, which cannot be explained by random fluctuations. The protein expression of one gene out of four of these bimodal genes tested, Gadd45a, exhibited clear inter-blastomeric contrasts. We traced some of the bimodal mRNA expressions to embryonic genome activation, and others to blastomere-specific RNA depletion. Interblastomere differences created coexpression gene networks that were much stronger and larger than those that can possibly be created by random noise. The highly correlated gene pairs at the 4-cell stage overlapped with those showing the same directions of differential expression between inner cell mass (ICM) and trophectoderm (TE). These data substantiate the hypothesis of inter-blastomere differences in 2-and 4-cell mouse embryos, and associate these differences with ICM/ TE differences.

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Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo

Cited by 243 publications

References 42 publications

Cell and molecular regulation of the mouse blastocyst

Cell and molecular regulation of the mouse blastocyst

Selective degradation of maternal and embryonic transcripts in in vitro produced bovine oocytes and embryos using sequence specific double-stranded RNA

Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing

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