scholarly journals BMP4 activates the Wnt-Lin28A-Blimp1-Wnt pathway to promote primordial germ cells formation via altering H3K4me2

2020 ◽  
pp. jcs.249375
Author(s):  
Qisheng Zuo ◽  
Kai Jin ◽  
Man Wang ◽  
Yani Zhang ◽  
Guohong Chen ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Formation Mechanism ◽  
Germ Cells ◽  
Positive Feedback ◽  
Gene Editing ◽  
Wnt Pathway ◽  
Primordial Germ Cells ◽  
Bird Species ◽  
Developmental Characteristics ◽  
Feedback Pathway

The unique developmental characteristics of Chicken primordial germ cells (PGCs) enable it to be used in recovery of endangered bird species, gene editing and the generation of transgenic birds, but the limited number of PGCs greatly limits its application. Studies have shown that the formation of mammalian PGCs is induced by BMP4 signal, but the formation mechanism of chicken PGCs has not been determined. Here, we confirmed that Wnt signaling activated via BMP4 activates transcription of Lin28A by inducing β-catenin to compete with LSD1 for binding to TCF7L2, causing LSD1 to dissociate from the Lin28A promoter and enhanced H3K4me2 methylation in this region. Lin28A promotes PGCs formation by inhibiting gga-let7a-3p maturation to initiate Blimp1 expression. Interestingly, expression of Blimp1 helped sustain Wnt5A expression by preventing LSD1 binding to the Wnt5A promoter. We thus elucidated a positive feedback pathway involving Wnt-Lin28-Blimp1-Wnt, that ensures PGCs formation. In summary, our data provide a new insights in the development of PGCs in chickens.

scholarly journals BMP4 Signaling Activates the Wnt-Lin28A-Blimp1-Wnt Positive Feedback Pathway to Promote Primordial Germ Cell Formation via Altering H3K4me2

2020 ◽  
Author(s):  
Qisheng Zuo ◽  
Yani Zhang ◽  
Guohong Chen ◽  
Bichun Li
Keyword(s):  
Wnt Signaling ◽  
Positive Feedback ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Cell Formation ◽  
Feedback System ◽  
Developmental Characteristics ◽  
Technical Basis ◽  
Feedback Pathway

Abstract (Background) The unique developmental characteristics of bird primordial germ cells (PGC) have enabled genetic engineering–based breeding and restoration of endangered birds via transplantation in vitro. However, the limited number of PGC has limited their application. Thus, there is an urgent need to elucidate the mechanism of PGC formation in vitro to enhance its efficiency. (Results) Here, we confirmed that activation of BMP4 and Wnt signaling (Wnt5A/β-catenin/TCF7L2) is critical for PGC formation via RNA-seq (ESCs, PGC and SSCs) and in vitro induction models. Wnt signaling activated via BMP4 in turn activates transcription of Lin28A by inducing β-catenin to compete with LSD1 for binding to the transcription factor TCF7L2, causing LSD1 to dissociate from the Lin28A promoter and enhanced H3K4me2 methylation in this region. Lin28A promotes PGC formation by inhibiting gga-let7a-3p maturation to initiate Blimp1 expression. Interestingly, expression of Blimp1 helped sustain Wnt5A expression by preventing LSD1 binding to the Wnt5A promoter. We thus elucidated a positive feedback pathway involving Wnt-Lin28-Blimp1-Wnt, with BMP4 functioning as an activator that ensures PGC formation. (Conclusion) In summary, our study clarified the molecular mechanism by which BMP4 and Wnt signaling regulate PGC formation via a positive feedback system. Our data provide both a theoretical and technical basis for studies aimed at enhancing the generation of PGC in vitro.

Localization of oskar RNA regulates oskar translation and requires Oskar protein

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2737-2746 ◽  
Author(s):  
C. Rongo ◽  
E.R. Gavis ◽  
R. Lehmann
Keyword(s):  
Germ Cells ◽  
Positive Feedback ◽  
Protein Localization ◽  
Primordial Germ Cells ◽  
Rna Localization ◽  
Feedback Mechanism ◽  
Posterior Pole ◽  
Translational Repression ◽  
Nonsense Mutations ◽  
Positive Feedback Mechanism

The site of oskar RNA and protein localization within the oocyte determines where in the embryo primordial germ cells form and where the abdomen develops. Initiation of oskar RNA localization requires the activity of several genes. We show that ovaries mutant for any of these genes lack Oskar protein. Using various transgenic constructs we have determined that sequences required for oskar RNA localization and translational repression map to the oskar 3′UTR, while sequences involved in the correct temporal activation of translation reside outside the oskar 3′UTR. Upon localization of oskar RNA and protein at the posterior pole, Oskar protein is required to maintain localization of oskar RNA throughout oogenesis. Stable anchoring of a transgenic reporter RNA at the posterior pole is disrupted by oskar nonsense mutations. We propose that initially localization of oskar RNA permits translation into Oskar protein and that subsequently Oskar protein regulates its own RNA localization through a positive feedback mechanism.

scholarly journals Germline Gene Editing in Chickens by Efficient CRISPR-Mediated Homologous Recombination in Primordial Germ Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0154303 ◽  
Author(s):  
Lazar Dimitrov ◽  
Darlene Pedersen ◽  
Kathryn H. Ching ◽  
Henry Yi ◽  
Ellen J. Collarini ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Germ Cells ◽  
Gene Editing ◽  
Primordial Germ Cells ◽  
Germline Gene

Production of Clone-like Chicken by Primordial Germ Cells Induced From Somatic Cells

2021 ◽  
Author(s):  
Ruifeng Zhao ◽  
Qisheng Zuo ◽  
Xia Yuan ◽  
Kai Jin ◽  
Yani Zhang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Somatic Cells ◽  
Bird Species ◽  
Unique Characteristic ◽  
Practical Application ◽  
Reprogramming Factors ◽  
First Time

Abstract The chicken primordial germ cell (PGCs) has the unique characteristic of settling in gonad through blood migration, which was the only way to realize the recovery of bird species. However, the PGCs obtained from a single embryo was far from enough to meet the practical application, while somatic cells can be obtained in large quantities. Therefore, the problem of insufficient PGCs can be solved by the induction of somatic cells into PGCs. Here, we successfully transdifferentiate somatic cells into PGCs, which can be transplanted to the recipient to produce offspring. In detail, The CEF of Black-Feathered Langshan Chicken was reprogrammed into iPS by reprogramming factors Oct4, Sox2, Nanog and Lin28, then was induced into PGCs by BMP4/BMP8b/EGF system. The induced PGCs has similar biological characteristics to the primary PGCs, which was transplanted into White Plymouth Rock Chicken, which self-crossed to produce clone-like offspring. It was the the first time to demonstrate the feasibility of avian cloning from somatic cells.

scholarly journals Precise CRISPR/Cas9 editing of the NHE1 gene renders chickens resistant to the J subgroup of avian leukosis virus

2020 ◽  
Vol 117 (4) ◽  
pp. 2108-2112 ◽  
Author(s):  
Anna Koslová ◽  
Pavel Trefil ◽  
Jitka Mucksová ◽  
Markéta Reinišová ◽  
Jiří Plachý ◽  
...  
Keyword(s):  
Germ Cells ◽  
Gene Editing ◽  
Primordial Germ Cells ◽  
Avian Leukosis Virus ◽  
Tryptophan Residue ◽  
Important Concern ◽  
Important Food Source

Avian leukosis virus subgroup J (ALV-J) is an important concern for the poultry industry. Replication of ALV-J depends on a functional cellular receptor, the chicken Na+/H+ exchanger type 1 (chNHE1). Tryptophan residue number 38 of chNHE1 (W38) in the extracellular portion of this molecule is a critical amino acid for virus entry. We describe a CRISPR/Cas9-mediated deletion of W38 in chicken primordial germ cells and the successful production of the gene-edited birds. The resistance to ALV-J was examined both in vitro and in vivo, and the ΔW38 homozygous chickens tested ALV-J–resistant, in contrast to ΔW38 heterozygotes and wild-type birds, which were ALV-J–susceptible. Deletion of W38 did not manifest any visible side effect. Our data clearly demonstrate the antiviral resistance conferred by precise CRISPR/Cas9 gene editing in the chicken. Furthermore, our highly efficient CRISPR/Cas9 gene editing in primordial germ cells represents a substantial addition to genotechnology in the chicken, an important food source and research model.

scholarly journals Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling

2016 ◽  
Vol 214 (2) ◽  
pp. 215-229 ◽  
Author(s):  
Andrea V. Cantú ◽  
Svetlana Altshuler-Keylin ◽  
Diana J. Laird
Keyword(s):  
Cell Cycle ◽  
Germ Cell ◽  
Wnt Signaling ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Early Embryo ◽  
Cell Pool ◽  
And Migration ◽  
Selective Mechanism ◽  
Proliferation And Migration

Inheritance depends on the expansion of a small number of primordial germ cells (PGCs) in the early embryo. Proliferation of mammalian PGCs is concurrent with their movement through changing microenvironments; however, mechanisms coordinating these conflicting processes remain unclear. Here, we find that PGC proliferation varies by location rather than embryonic age. Ror2 and Wnt5a mutants with mislocalized PGCs corroborate the microenvironmental regulation of the cell cycle, except in the hindgut, where Wnt5a is highly expressed. Molecular and genetic evidence suggests that Wnt5a acts via Ror2 to suppress β-catenin–dependent Wnt signaling in PGCs and limit their proliferation in specific locations, which we validate by overactivating β-catenin in PGCs. Our results suggest that the balance between expansion and movement of migratory PGCs is fine-tuned in different niches by the opposing β-catenin–dependent and Ror2-mediated pathways through Wnt5a. This could serve as a selective mechanism to favor early and efficient migrators with clonal dominance in the ensuing germ cell pool while penalizing stragglers.

scholarly journals Avian Primordial Germ Cells Are Bipotent for Male or Female Gametogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Maeve Ballantyne ◽  
Lorna Taylor ◽  
Tuanjun Hu ◽  
Dominique Meunier ◽  
Sunil Nandi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Bird Species ◽  
Male Sterile ◽  
Cell Competition ◽  
Germ Cell Differentiation ◽  
Heterogametic Sex

In birds, males are the homogametic sex (ZZ) and females are the heterogametic sex (ZW). Here, we investigate the role of chromosomal sex and germ cell competition on avian germ cell differentiation. We recently developed genetically sterile layer cockerels and hens for use as surrogate hosts for primordial germ cell (PGC) transplantation. Using in vitro propagated and cryopreserved PGCs from a pedigree Silkie broiler breed, we now demonstrate that sterile surrogate layer hosts injected with same sex PGCs have normal fertility and produced pure breed Silkie broiler offspring when directly mated to each other in Sire Dam Surrogate mating. We found that female sterile hosts carrying chromosomally male (ZZ) PGCs formed functional oocytes and eggs, which gave rise to 100% male offspring after fertilization. Unexpectedly, we also observed that chromosomally female (ZW) PGCs carried by male sterile hosts formed functional spermatozoa and produced viable offspring. These findings demonstrate that avian PGCs are not sexually restricted for functional gamete formation and provide new insights for the cryopreservation of poultry and other bird species using diploid stage germ cells.

Hexachlorobenzene toxicity in the rat ovary: II. Ultrastructure induced by medium (10 mg/kg) dose exposure

1992 ◽  
Vol 50 (1) ◽  
pp. 668-669
Author(s):  
Amreek Singh ◽  
Warren G. Foster ◽  
Anna Dykeman ◽  
David C. Villeneuve
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells ◽  
Surface Epithelium ◽  
Morphological Parameters ◽  
Comprehensive Investigation ◽  
Ovary Surface Epithelium ◽  
Rat Ovary ◽  
High Doses

Hexachlorobenzene (HCB) is a known toxicant that is found in the environment as a by-product during manufacture of certain pesticides. This chlorinated chemical has been isolated from many tissues including ovary. When administered in high doses, HCB causes degeneration of primordial germ cells and ovary surface epithelium in sub-human primates. A purpose of this experiment was to determine a no-effect dose of the chemical on the rat ovary. The study is part of a comprehensive investigation on the effects of the compound on the biochemical, hematological, and morphological parameters in the monkey and rat.

Transfusion of Chick Primordial Germ Cells into Quail Embryos and their Settlement in Gonads

1998 ◽  
Vol 69 (10) ◽  
pp. 911-915 ◽  
Author(s):  
Tamao ONO ◽  
Ryohei YOKOI ◽  
Seishi MAEDA ◽  
Takao NISHIDA ◽  
Hirohiko AOYAMA
Keyword(s):  
Germ Cells ◽  
Primordial Germ Cells
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