Dynamics of Known Long Non-Coding RNAs during the Maternal-to-Zygotic Transition in Rabbit

The control of pre-implantation development in mammals undergoes a maternal-to-zygotic transition (MZT) after fertilization. The transition involves maternal clearance and zygotic genome activation remodeling the terminal differentiated gamete to confer totipotency. In the study, we first determined the profile of long non-coding RNAs (lncRNAs) of mature rabbit oocyte, 2-cell, 4-cell, 8-cell, and morula embryos using RNA-seq. A total of 2673 known rabbit lncRNAs were identified. The lncRNAs exhibited dynamic expression patterns during pre-implantation development. Moreover, 107 differentially expressed lncRNAs (DE lncRNAs) were detected between mature oocyte and 2-cell embryo, while 419 DE lncRNAs were detected between 8-cell embryo and morula, consistent with the occurrence of minor and major zygotic genome activation (ZGA) wave of rabbit pre-implanted embryo. This study then predicted the potential target genes of DE lncRNAs based on the trans-regulation mechanism of lncRNAs. The GO and KEGG analyses showed that lncRNAs with stage-specific expression patterns promoted embryo cleavage and synchronic development by regulating gene transcription and translation, intracellular metabolism and organelle organization, and intercellular signaling transduction. The correlation analysis between mRNAs and lncRNAs identified that lncRNAs ENSOCUG00000034943 and ENSOCUG00000036338 may play a vital role in the late-period pre-implantation development by regulating ILF2 gene. This study also found that the sequential degradation of maternal lncRNAs occurred through maternal and zygotic pathways. Furthermore, the function analysis of the late-degraded lncRNAs suggested that these lncRNAs may play a role in the mRNA degradation in embryos via mRNA surveillance pathway. Therefore, this work provides a global view of known lncRNAs in rabbit pre-implantation development and highlights the role of lncRNAs in embryogenesis regulation.

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Dux facilitates post-implantation development, but is not essential for zygotic genome activation†

Biology of Reproduction ◽

10.1093/biolre/ioaa179 ◽

2020 ◽

Author(s):

Darko Bosnakovski ◽

Micah D Gearhart ◽

Si Ho Choi ◽

Michael Kyba

Keyword(s):

Target Genes ◽

Homeobox Gene ◽

Zygotic Genome Activation ◽

Placental Development ◽

Blastocyst Development ◽

Cell Embryo ◽

Genome Activation ◽

Post Implantation ◽

Zygotic Genome

Abstract Double homeobox genes are unique to eutherian mammals. It has been proposed that the DUXC clade of the double homeobox gene family, which is present in multicopy long tandem arrays, plays an essential role in zygotic genome activation (ZGA). We generated a deletion of the tandem array encoding the DUXC gene of mouse, Double homeobox (Dux), and found it surprisingly to be homozygous viable and fertile. We characterize the embryonic development and ZGA profile of knockout (KO) embryos, finding that zygotic genome activation still occurs, with only modest alterations in 2-cell embryo gene expression, no defect in in vivo preimplantation development, but an increased likelihood of post-implantation developmental failure, leading to correspondingly smaller litter sizes in the KO strain. While all known 2-cell specific Dux target genes are still expressed in the KO, a subset is expressed at lower levels. These include numerous genes involved in methylation, blastocyst development, and trophectoderm/placental development. We propose that rather than driving ZGA, which is a process common throughout the animal kingdom, DUXC genes facilitate a process unique to eutherian mammals, namely the post-implantation development enabled by an invasive placenta.

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Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.788512 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yuanyuan Li ◽

Ning-Hua Mei ◽

Gui-Ping Cheng ◽

Jing Yang ◽

Li-Quan Zhou

Keyword(s):

Embryo Development ◽

Preimplantation Embryo ◽

Preimplantation Embryos ◽

Dependent Manner ◽

Zygotic Genome Activation ◽

Preimplantation Embryo Development ◽

Cell Embryo ◽

Embryo Stage ◽

Genome Activation ◽

Zygotic Genome

Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.

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DPPA2 and DPPA4 are dispensable for mouse zygotic genome activation and preimplantation development

10.1101/2021.08.19.457017 ◽

2021 ◽

Author(s):

Zhiyuan Chen ◽

Zhenfei Xie ◽

Yi Zhang

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Embryonic Stem ◽

Preimplantation Development ◽

Dependent Manner ◽

Maternal Factors ◽

Zygotic Genome Activation ◽

Cell Embryo ◽

Genome Activation ◽

Zygotic Genome

How maternal factors in oocytes initiate zygotic genome activation (ZGA) remains elusive. Recent studies indicate that DPPA2 and DPPA4 are required for establishing a 2-cell embryo-like (2C-like) state in mouse embryonic stem cells (ESCs) in a DUX-dependent manner. These results suggest that DPPA2 and DPPA4 are essential maternal factors that regulate Dux and ZGA in embryos. By analyzing maternal knockout and maternal-zygotic knockout embryos, we unexpectedly found that Dux activation, ZGA, and preimplantation development are normal in embryos without DPPA2 or DPPA4. Thus, unlike in ESCs/2C-like cells, DPPA2 and DPPA4 are dispensable for ZGA and preimplantation development.

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MiR-290 family maintains developmental potential by targeting p21 in mouse pre-implantation embryos

Biology of Reproduction ◽

10.1093/biolre/ioab227 ◽

2021 ◽

Author(s):

Xiangnan Li ◽

Yueshi Liu ◽

Qier Mu ◽

Junliang Tian ◽

Haiquan Yu

Keyword(s):

Embryonic Development ◽

Untranslated Region ◽

Target Genes ◽

Embryonic Stem ◽

Blastocyst Stage ◽

Developmental Potential ◽

Cell Embryo ◽

Embryo Stage ◽

Genome Activation ◽

Zygotic Genome

Abstract The miR-290 family is a mouse-specific microRNA cluster, which maintains mouse embryonic stem cells (ESCs) pluripotency by increasing OCT3/4 and C-MYC expression. However, its functions in mouse pre-implantation embryos remain unclear, especially during zygotic genome activation (ZGA). In this study, miR-290 family expression increased from the two-cell embryo stage through the blastocyst stage. Inhibition of miR-294-3p/5p did not affect ZGA initiation or embryo development, whereas pri-miR-290 knockdown decreased ZGA gene expression and slowed embryonic development. In addition, pluripotency decreased in ESCs derived from pri-miR-290 knockdown blastocysts. To clarify the mechanism of action, 33 candidate miR-294-3p target genes were screened from three databases, and miR-294-3p directly targeted the 3′-untranslated region of Cdkn1a (p21) mRNA. Similar to pri-miR-290 knockdown, P21 overexpression impeded embryonic development, whereas simultaneous overexpression of P21 and pri-miR-290 partially rescued embryonic development. The results indicate that the miR-290 family participates in promoting ZGA process and maintaining developmental potency in embryos by targeting p21.

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Transcriptional Activation of Arabidopsis Zygotes Is Required for Initial Cell Divisions

Scientific Reports ◽

10.1038/s41598-019-53704-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 15

Author(s):

Ping Kao ◽

Michael D. Nodine

Keyword(s):

Transcriptional Activation ◽

Gene Products ◽

Zygotic Genome Activation ◽

Microscopy Technique ◽

Early Embryos ◽

Maternal To Zygotic Transition ◽

Parental Gene ◽

Active Transcription ◽

Genome Activation ◽

Zygotic Genome

AbstractCommonly referred to as the maternal-to-zygotic transition, the shift of developmental control from maternal-to-zygotic genomes is a key event during animal and plant embryogenesis. Together with the degradation of parental gene products, the increased transcriptional activities of the zygotic genome remodels the early embryonic transcriptome during this transition. Although evidence from multiple flowering plants suggests that zygotes become transcriptionally active soon after fertilization, the timing and developmental requirements of zygotic genome activation in Arabidopsis thaliana (Arabidopsis) remained a matter of debate until recently. In this report, we optimized an expansion microscopy technique for robust immunostaining of Arabidopsis ovules and seeds. This enabled the detection of marks indicative of active transcription in zygotes before the first cell division. Moreover, we employed a live-imaging culture system together with transcriptional inhibitors to demonstrate that such active transcription is physiologically required in zygotes and early embryos. Our results indicate that zygotic genome activation occurs soon after fertilization and is required for the initial zygotic divisions in Arabidopsis.

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Transcriptional Activation of Arabidopsis Zygotes Is Required for Their Initial Division

10.1101/679035 ◽

2019 ◽

Author(s):

Ping Kao ◽

Michael Nodine

Keyword(s):

Transcriptional Activation ◽

Culture System ◽

Gene Products ◽

Zygotic Genome Activation ◽

Microscopy Technique ◽

Maternal To Zygotic Transition ◽

Parental Gene ◽

Active Transcription ◽

Genome Activation ◽

Zygotic Genome

SUMMARYCommonly referred to as the maternal-to-zygotic transition, the shift of developmental control from maternal-to-zygotic genomes is a key event during animal and plant embryogenesis. Together with the degradation of parental gene products, the increased transcriptional activities of the zygotic genome remodels the early embryonic transcriptome during this transition. Although evidence from multiple flowering plants suggests that zygotes become transcriptionally active soon after fertilization, the timing and developmental requirements of zygotic genome activation in Arabidopsis thaliana (Arabidopsis) remained a matter of debate until recently. In this report, we optimized an expansion microscopy technique for robust immunostaining of Arabidopsis ovules and seeds. This enabled the detection of marks indicative of active transcription in zygotes before the first cell division. Moreover, we employed a live-imaging culture system together with transcriptional inhibitors to demonstrate that such active transcription is required in zygotes. Our results indicate that zygotic genome activation occurs soon after fertilization and is physiologically required prior to the initial zygotic division in Arabidopsis.

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Expression and localization of Nlrp4g in mouse preimplantation embryo

Zygote ◽

10.1017/s0967199414000525 ◽

2014 ◽

Vol 23 (6) ◽

pp. 846-851 ◽

Cited By ~ 2

Author(s):

Hui Peng ◽

Xiujiao Lin ◽

Wenhao Li ◽

Wenchang Zhang

Keyword(s):

Preimplantation Embryo ◽

Expression Patterns ◽

Blastocyst Stage ◽

Preimplantation Embryo Development ◽

Gene Copies ◽

Mouse Preimplantation Embryo ◽

Cell Embryo ◽

Embryo Stage ◽

Genome Activation ◽

Zygotic Genome

SummaryThe Nlrp gene family contains 20 members and plays a pivotal role in the innate immune and reproductive systems in the mouse. During evolution, seven Nlrp4 gene copies (named from Nlrp4a to Nlrp4g). Nlrp4a–Nlrp4g have arisen that display specific or preferential ovarian expression patterns. However, the expression pattern and localization of Nlrp4g in mouse preimplantation embryo development are unknown. Here we report that Nlrp4g was highly expressed in mature oocytes and zygotes, then downregulated and not detected after the 2-cell embryo stage. NLRP4G protein remained present through the blastocyst stage and was mainly localized in the cytoplasm. Furthermore, overexpression of Nlrp4g in zygotes did not affect normal development in terms of the rate of blastocyst formation. These results provide the first evidence that NLRP4G is a maternal factor that may play essential role during zygotic genome activation in the mouse.

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