Cell Polarity Regulator PARD6B Is Essential for Trophectoderm Formation in the Preimplantation Mouse Embryo1

Alarcón, Vernadeth B.

doi:10.1095/biolreprod.110.084400

Cited by 135 publications

(142 citation statements)

References 54 publications

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“…Trophectoderm-specific expression of Cdx2 is mediated by the establishment of apical cell polarity and position-dependent HIPPO signaling during the 8-cell to morula and morula to blastocyst transitions, respectively (Alarcon, 2010;Hirate et al, 2013). We previously showed that Pard6b is a direct target gene of TFAP2C in preimplantation embryos and TS-like cells (Choi et al, 2012).…”

Section: Tfap2c Regulates Apical Cell Polarity Via Pard6bmentioning

confidence: 99%

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

et al. 2015

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Cell fate decisions are fundamental to the development of multicellular organisms. In mammals the first cell fate decision involves segregation of the pluripotent inner cell mass and the trophectoderm, a process regulated by cell polarity proteins, HIPPO signaling and lineagespecific transcription factors such as CDX2. However, the regulatory mechanisms that operate upstream to specify the trophectoderm lineage have not been established. Here we report that transcription factor AP-2γ (TFAP2C) functions as a novel upstream regulator of Cdx2 expression and position-dependent HIPPO signaling in mice. Loss-and gain-of-function studies and promoter analysis revealed that TFAP2C binding to an intronic enhancer is required for activation of Cdx2 expression during early development. During the 8-cell to morula transition TFAP2C potentiates cell polarity to suppress HIPPO signaling in the outside blastomeres. TFAP2C depletion triggered downregulation of PARD6B, loss of apical cell polarity, disorganization of F-actin, and activation of HIPPO signaling in the outside blastomeres. Rescue experiments using Pard6b mRNA restored cell polarity but only partially corrected position-dependent HIPPO signaling, suggesting that TFAP2C negatively regulates HIPPO signaling via multiple pathways. Several genes involved in regulation of the actin cytoskeleton (including Rock1, Rock2) were downregulated in TFAP2C-depleted embryos. Inhibition of ROCK1 and ROCK2 activity during the 8-cell to morula transition phenocopied TFAP2C knockdown, triggering a loss of position-dependent HIPPO signaling and decrease in Cdx2 expression. Altogether, these results demonstrate that TFAP2C facilitates trophectoderm lineage specification by functioning as a key regulator of Cdx2 transcription, cell polarity and position-dependent HIPPO signaling.

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Section: Tfap2c Regulates Apical Cell Polarity Via Pard6bmentioning

confidence: 99%

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

et al. 2015

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“…Recent studies show that developmental paucity of experimentally manipulated embryos can be "rescued" by culturing from the 8-cell stage in ESCM [31,76]. Such manipulations include the knockdown of Pard6b and Cdx2 genes by injection of RNA interference agents, which severely compromises embryo development in KSOM.…”

Section: Discussionmentioning

confidence: 99%

“…Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) RNA extraction from blastocysts, cDNA synthesis, and real-time PCR using the specific β-actin, Gapdh, Oct4 and Cdx2 primers were performed as previously described [31].…”

Section: Embryo Culturementioning

confidence: 99%

A potential use of embryonic stem cell medium for the in vitro culture of preimplantation embryos

Gelber

Tamura

Alarcón

et al. 2011

J Assist Reprod Genet

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Purpose To assess the impact of embryonic stem cell culture medium (ESCM) on the pre-and postimplantation development of the mouse embryo, as a mammalian model, in comparison with the conventional culture medium, a potassium simplex optimized medium (KSOM). Methods Development in ESCM versus KSOM was compared in terms of embryo morphology, cleavage, cavitation, hatching, cell number, expression of TE and ICM transcription factors (Cdx2 and Oct4, respectively), implantation, and development in utero.

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“…In the mouse embryo, Par3 and aPKC homologs regulate the orientation of cell cleavage planes as well as cell polarity and adhesion, which together can influence the allocation of blastomeres to an outer or inner position in the blastocyst. Par6 is essential for normal blastocyst formation in the mouse embryo [58]. Par6 gene knockdown resulted in cavitation failure without compromising blastomere cleavage or compaction by abnormal epithelial junctions, which then lead to defective paracellular permeability sealing in the outer cells of the embryo.…”

Section: Morulamentioning

confidence: 99%

Protein Profile Involved in Mammalian Oocyte Maturation, Fertilization and Early Embryogenesis (Pre-Implantation)

Turathum¹,

Sroyraya²

2017

Cell Dev Biol

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Proteomic analysis of oocytes can help identify proteins that are involved in female meiotic maturation and early embryonic development. Many proteins with well-defined functions have been identified during oocyte maturation. High levels of MPF, MAPK, Mos and low levels of cAMP play an essential role in the resumption of meiosis I. Following germinal vesicle breakdown, chromosome condensation and spindle formation occurred at metaphase I by assembly of the meiotic apparatus, which includes the proteins NuMA, γ-tubulin and Polo-like kinase 1. The metaphase II arrest is a result of high levels of MPF and MAPK. Proteins involved in the stress response and redox regulation, including peroxiredoxin, GST and HSF1, are also necessary for protection against oxidative stress. During fertilization, the sperm-egg interaction requires egg surface proteins, oocyte zona pellucida, molecular chaperones, GPI-anchored proteins and CD9 to recognize sperm proteins and prevent polyspermy. Following gamete fusion, resumption and complete of meiosis II is induced by GTP and CaM kinase II activation, which inactivates MPF and activation of the anaphase promoting complex/cyclosome results in sister chromatid separation. Decondensation of the sperm head begins after zona penetration and GSH and NPM2 are necessary for male pronuclear formation. MAPK inactivation is required for pronuclear formation. At the cleavage stage, the maternal effect proteins PADI6, FLOPED and FILIA are essential for embryonic progression past the two-cell stage. After cell adhesion, cell junctions and the cytoskeleton play an important role in compaction of the morula. Par6, Par3 and protein kinase C are components of the apical polarity complex and are important for formation of the blastocoel cavity. During the blastocyst stage, TEAD4 and CDX2 are required for trophoectoderm formation. This proteomic analysis of oocytes has improved our understanding of the molecular processes that regulate oocyte maturation, fertilization and pre-implantation in mammals.

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Cell Polarity Regulator PARD6B Is Essential for Trophectoderm Formation in the Preimplantation Mouse Embryo1

Cited by 135 publications

References 54 publications

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

A potential use of embryonic stem cell medium for the in vitro culture of preimplantation embryos

Protein Profile Involved in Mammalian Oocyte Maturation, Fertilization and Early Embryogenesis (Pre-Implantation)

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