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zygote arrest 1 OKDB#: 1716
 Symbols: ZAR1 Species: human
 Synonyms: Z3CXXC6  Locus: 4p11 in Homo sapiens


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General Comment Wu X, et al 2003 reported that Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition. To understand these processes further, the authors identified genes called zygote arrest 1 (Zar1 and ZAR1 in mouse and human, respectively) as novel oocyte-specific genes. These encode proteins of 361 amino acids and 424 amino acids, respectively, which share 59% amino-acid identity and an atypical plant homeo-domain (PHD) motif. Although Zar1-null (Zar1(-/-)) mice are viable and grossly normal, Zar1(-/-) females are infertile. Ovarian development and oogenesis through the early stages of fertilization are evidently unimpaired, but most embryos from Zar1(-/-) females arrest at the one-cell stage. Distinct pronuclei form and DNA replication initiates, but the maternal and paternal genomes remain separate in arrested zygotes. Fewer than 20% of the embryos derived from Zar1(-/-) females progress to the two-cell stage and show marked reduction in the synthesis of the transcription-requiring complex, and no embryos develop to the four-cell stage. Thus, Zar1 is the first identified oocyte-specific maternal-effect gene that functions at the oocyte-to-embryo transition and, as such, offers new insights into the initiation of embryonic development and fertility control in mammals.This is a maternal effect gene.

NCBI Summary: This maternal effect gene is oocyte-specific and encodes a protein that is thought to function in the initiation of embryogenesis. A similar protein in mouse is required for female fertility. [provided by RefSeq, Jul 2013]
General function
Comment
Cellular localization Nuclear
Comment
Ovarian function Oocyte maturation, Early embryo development
Comment
Expression regulated by
Comment
Ovarian localization Oocyte
Comment Zygote arrest 1, nucleoplasmin 2, and developmentally associated protein 3 mRNA profiles throughout porcine embryo development in vitro. Wasielak M et al. (2016) Maternal effect genes (MEGs) are expressed in oocytes and embryos and play an important role in activation of the embryonic genome. An abnormality in the expression of these genes may lead to arrest of embryonic cleavage or to altered transcription of factors responsible for further embryonic development. In vitro-produced porcine embryos have a lower developmental potential than embryos produced in vivo. We hypothesized that in vitro embryo culture conditions have an effect on the expression of MEGs at various developmental stages, which may affect their developmental potential. Here, using real-time polymerase chain reaction, we examined mRNA profiles of the MEGs, zygote arrest 1 (ZAR-1), nucleoplasmin 2 (NPM2), and developmentally associated pluripotency protein 3 (DPPA3), in porcine oocytes and embryos produced in vitro and in vivo. Further, we evaluated the effect of the combined addition of EGF, interleukin 1β, and leukemia inhibitory factor to the porcine in vitro embryo production system on mRNA profiles of selected MEGs. Finally, we studied localization of the MEG protein products in in vitro-obtained oocytes and embryos using confocal microscopy. We found that the ZAR-1 mRNA profile differed throughout in vitro and in vivo embryo development. In the embryos produced in vitro, the decrease in ZAR-1 mRNA levels was observed at the 2-cell stage, whereas in in vivo embryos, ZAR-1 mRNA levels declined significantly starting at the 4-cell stage (P < 0.05). In vitro culture conditions affected transiently also DPPA3 mRNA levels at the 4-cell stage (P < 0.05). There was no difference in the NPM2 mRNA profile during in vitro and in vivo embryo development. The ZAR-1 and DPPA3 proteins were localized in the cytoplasm of the oocytes and embryos, whereas the NPM2 protein was found both in the cytoplasm and in the nucleus. All proteins were expressed until blastocyst stage. The addition of EGF and cytokines to the culture medium decreased DPPA3 mRNA levels in 8-cell embryos (P < 0.05). This study indicated that IVC conditions affect ZAR-1 mRNA levels before the 4-cell stage, which may disturb the activation of the embryonic genome in pigs. The expression of the proteins after the 4-cell to 8-cell transition indicates that these factors play a role beyond activation of the embryonic genome. Supplementation of the culture media with EGF and cytokines affects DPPA3 mRNA levels after maternal to embryonic transition.////////////////// Expression of chicken zygote arrest 1 (Zar1) and Zar1-like genes during sexual maturation and embryogenesis. Michailidis G et al. Maternal mRNAs, which are expressed in oocytes, play an important role in the success of early embryo development, as they allow the first cleavages to occur. Zygote arrest 1 (Zar1) is an oocyte-specific maternal-effect gene that functions at the oocyte-to-embryo transition in many vertebrate species including human, pig, cattle, sheep, mouse, rat, frog and zebrafish. Recently, through in silico studies, a gene structurally related to Zar1, called Zar1-like has been identified in many vertebrates, including the chicken. The objectives of this study were to investigate the expression of the chicken Zar1 and Zar1-like genes in chicken tissues and embryos and to determine whether sexual maturation affects their mRNA abundance. RNA was extracted from various organs of chickens aged from one month up to two years old and from chicken embryos until day ten of embryonic development. Expression analysis of the genes was performed using RT-PCR and real-time PCR. RT-PCR analysis revealed that both genes were preferentially expressed in chicken oocytes, ovary and testes and in embryos during embryonic development. Quantitative real-time PCR analysis revealed a significant up regulation of Zar1 in the mature ovary, and also a significant up regulation of Zar1 and Zar1-like genes in the testes of sexually mature roosters, suggesting a key role of these genes in the chicken fertility. In contrast, expression of Zar1-like was not affected by age in the chicken ovary. Our results indicate that the chicken Zar1 and Zar1-like transcripts are co-expressed in high levels in the chicken gonads. In addition their expression beyond the stage of embryonic genome activation suggests an embryonic and not only a maternal origin of these transcripts.
Follicle stages Antral, Preovulatory
Comment
Phenotypes
Mutations 3 mutations

Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Wu X, et al 2003 reported that Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition. Although Zar1-null (Zar1(-/-)) mice are viable and grossly normal, Zar1(-/-) females are infertile. Ovarian development and oogenesis through the early stages of fertilization are evidently unimpaired, but most embryos from Zar1(-/-) females arrest at the one-cell stage. Distinct pronuclei form and DNA replication initiates, but the maternal and paternal genomes remain separate in arrested zygotes. Fewer than 20% of the embryos derived from Zar1(-/-) females progress to the two-cell stage and show marked reduction in the synthesis of the transcription-requiring complex, and no embryos develop to the four-cell stage. Thus, Zar1 is the first identified oocyte-specific maternal-effect gene that functions at the oocyte-to-embryo transition and, as such, offers new insights into the initiation of embryonic development and fertility control in mammals.

Species: other
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Translation repression by maternal RNA binding protein zar1 is essential for early oogenesis in zebrafish. Miao L et al. (2016) Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNAs in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants which result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development. zar1 immature ovaries show upregulation of proteins implicated in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). More importantly, loss of Zar1 causes markedly upregulation of zona pellucida (ZP) family proteins, while overexpression of ZP proteins in oocytes causes upregulation of stress related activating transcription factor 3 (atf3), arguing that tightly controlled translation of ZP proteins is essential for ER homeostasis during early oogenesis. Furthermore, Zar1 binds to zona pellucida (zp) mRNAs and represses their translation. Together our results indicate that regulation of translational repression and de-repression are essential for precisely controlling protein expression during early oogenesis.//////////////////

Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation. Rong Y et al. (2020) Zar1 was one of the earliest mammalian maternal-effect genes to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oocyte meiotic maturation. Zar1/2-deleted oocytes displayed delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy. The grown oocytes of Zar1/2-null mice contained decreased levels of many maternal mRNAs and displayed a reduced level of protein synthesis. Key maturation-associated changes failed to occur in the Zar1/2-null oocytes, including the translational activation of maternal mRNAs encoding the cell-cycle proteins cyclin B1 and WEE2, as well as maternal-to-zygotic transition (MZT) licensing factor BTG4. Consequently, maternal mRNA decay was impaired and MZT was abolished. ZAR1/2 bound mRNAs to regulate the translational activity of their 3'-UTRs and interacted with other oocyte proteins, including mRNA-stabilizing protein MSY2 and cytoplasmic lattice components. These results countered the traditional view that ZAR1 only functions after fertilization and highlight a previously unrecognized role of ZAR1/2 in regulating the maternal transcriptome and translational activation in maturing oocytes.//////////////////

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created: Feb. 14, 2003, 6:06 a.m. by: hsueh   email:
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last update: May 5, 2020, 12:48 p.m. by: hsueh    email:



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