scholarly journals Mammalian primordial germ cell specification

Development ◽  
2021 ◽  
Vol 148 (6) ◽  
Author(s):  
Grace V. Hancock ◽  
Sissy E. Wamaitha ◽  
Lior Peretz ◽  
Amander T. Clark
Keyword(s):  
Germ Cell ◽  
Molecular Mechanisms ◽  
Primordial Germ Cell ◽  
Model Organisms ◽  
Mammalian Development ◽  
Mouse Development ◽  
Implantation Window ◽  
Germ Cell Specification ◽  
Developmental Divergence

ABSTRACT The peri-implantation window of mammalian development is the crucial window for primordial germ cell (PGC) specification. Whereas pre-implantation dynamics are relatively conserved between species, the implantation window marks a stage of developmental divergence between key model organisms, and thus potential variance in the cell and molecular mechanisms for PGC specification. In humans, PGC specification is very difficult to study in vivo. To address this, the combined use of human and nonhuman primate embryos, and stem cell-based embryo models are essential for determining the origin of PGCs, as are comparative analyses to the equivalent stages of mouse development. Understanding the origin of PGCs in the peri-implantation embryo is crucial not only for accurate modeling of this essential process using stem cells, but also in determining the role of global epigenetic reprogramming upon which sex-specific differentiation into gametes relies.

scholarly journals Human blastocyst outgrowths recapitulate primordial germ cell specification events

2019 ◽  
Vol 25 (9) ◽  
pp. 519-526 ◽  
Author(s):  
Mina Popovic ◽  
Monika Bialecka ◽  
Maria Gomes Fernandes ◽  
Jasin Taelman ◽  
Margot Van Der Jeught ◽  
...  
Keyword(s):  
Germ Cell ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Descriptive Analysis ◽  
Primordial Germ Cell ◽  
Human Embryos ◽  
Embryo Viability ◽  
Germ Cell Specification

Abstract Our current knowledge of the mechanisms leading to human primordial germ cell (PGC) specification stems solely from differentiation experiments starting from human pluripotent stem cells. However, information regarding the origin of PGCs in vivo remains obscure. Here we apply an improved system for extended in vitro culture of human embryos to investigate the presence of PGC-like cells (PGCLCs) 12 days post fertilization (dpf). Good quality blastocysts (n = 141) were plated at 6 dpf and maintained in hypoxia, in medium supplemented with Activin A until 12 dpf. We primarily reveal that 12 dpf outgrowths recapitulate human peri-implantation events and demonstrate that blastocyst quality significantly impacts both embryo viability at 12 dpf, as well as the presence of POU5F1+ cells within viable outgrowths. Moreover, detailed examination of 12 dpf blastocyst outgrowths revealed a population of POU5F1+, SOX2– and SOX17+ cells that may correspond to PGCLCs, alongside POU5F1+ epiblast-like cells and GATA6+ endoderm-like cells. Our findings suggest that, in human, PGC precursors may become specified within the epiblast and migrate either transiently to the extra-embryonic mesoderm or directly to the dorsal part of the yolk sac endoderm around 12 dpf. This is a descriptive analysis and as such the conclusion that POU5F1+ and SOX17+ cells represent bona fide PGCs can only be considered as preliminary. In the future, other PGC markers may be used to further validate the observed cell populations. Overall, our findings provide insights into the origin of the human germline and may serve as a foundation to further unravel the molecular mechanisms governing PGC specification in human.

scholarly journals Blimp-1/Prdm1 Alternative Promoter Usage during Mouse Development and Plasma Cell Differentiation

2009 ◽  
Vol 29 (21) ◽  
pp. 5813-5827 ◽  
Author(s):  
Marc A. J. Morgan ◽  
Erna Magnusdottir ◽  
Tracy C. Kuo ◽  
Chai Tunyaplin ◽  
James Harper ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Plasma Cell ◽  
Primordial Germ Cell ◽  
Alternative Promoter ◽  
Start Codon ◽  
Mouse Development ◽  
Noticeable Effect ◽  
Plasma Cell Differentiation ◽  
Germ Cell Specification

ABSTRACT The zinc-finger PR domain transcriptional repressor Blimp-1/Prdm1 plays essential roles in primordial germ cell specification, placental, heart, and forelimb development, plasma cell differentiation, and T-cell homeostasis. The present experiments demonstrate that the mouse Prdm1 gene has three alternative promoter regions. All three alternative first exons splice directly to exon 3, containing the translational start codon. To examine possible cell-type-specific functional activities in vivo, we generated targeted deletions that selectively eliminate two of these transcriptional start sites. Remarkably, mice lacking the previously described first exon develop normally and are fertile. However, this region contains NF-κB binding sites, and as shown here, NF-κB signaling is required for Prdm1 induction. Thus, mutant B cells fail to express Prdm1 in response to lipopolysaccharide stimulation and lack the ability to become antibody-secreting cells. An alternative distal promoter located ∼70 kb upstream, giving rise to transcripts strongly expressed in the yolk sac, is dispensable. Thus, the deletion of exon 1B has no noticeable effect on expression levels in the embryo or adult tissues. Collectively, these experiments provide insight into the organization of the Prdm1 gene and demonstrate that NF-κB is a key mediator of Prdm1 expression.

Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation

Development ◽  
2001 ◽  
Vol 128 (18) ◽  
pp. 3609-3621 ◽  
Author(s):  
Kimberly D. Tremblay ◽  
N. Ray Dunn ◽  
Elizabeth J. Robertson
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Es Cells ◽  
Primordial Germ Cells ◽  
Primordial Germ Cell ◽  
Mouse Embryos ◽  
Visceral Endoderm ◽  
Mouse Development ◽  
Embryonic Tissues ◽  
Germ Cell Specification

The Smad proteins are important intracellular mediators of the transforming growth factor β (TGFβ) family of secreted growth factors. Smad1 is an effector of signals provided by the bone morphogenetic protein (BMP) sub-group of TGFβ molecules. To understand the role of Smad1 in mouse development, we have generated a Smad1 loss-of-function allele using homologous recombination in ES cells. Smad1−/− embryos die by 10.5 dpc because they fail to connect to the placenta. Mutant embryos are first recognizable by 7.0 dpc, owing to a characteristic localized outpocketing of the visceral endoderm at the posterior embryonic/extra-embryonic junction, accompanied by a dramatic twisting of the epiblast and nascent mesoderm. Chimera analysis reveals that these two defects are attributable to a requirement for Smad1 in the extra-embryonic tissues. By 7.5 dpc, Smad1-deficient embryos show a marked impairment in allantois formation. By contrast, the chorion overproliferates, is erratically folded within the extra-embryonic space and is impeded in proximal migration. BMP signals are known to be essential for the specification and proliferation of primordial germ cells. We find a drastic reduction of primordial germ cells in Smad1-deficient embryos, suggesting an essential role for Smad1-dependent signals in primordial germ cell specification. Surprisingly, despite the key involvement of BMP signaling in tissues of the embryo proper, Smad1-deficient embryos develop remarkably normally. An examination of the expression domains of Smad1, Smad5 and Smad8 in early mouse embryos show that, while Smad1 is uniquely expressed in the visceral endoderm at 6.5 dpc, in other tissues Smad1 is co-expressed with Smad5 and/or Smad8. Collectively, these data have uncovered a unique function for Smad1 signaling in coordinating the growth of extra-embryonic structures necessary to support development within the uterine environment.

Developmental stages, incubation temperature, and in vivo traceability of primordial germ cell in an important aquaculture species Piaractus mesopotamicus

Aquaculture ◽  
2021 ◽  
Vol 535 ◽  
pp. 736381
Author(s):  
Geovanna Carla Zacheo Coelho ◽  
Dilberto Ribeiro Arashiro ◽  
Tamiris Disselli ◽  
Matheus Pereira-Santos ◽  
Tatiana María Mira-López ◽  
...  
Keyword(s):  
Germ Cell ◽  
Developmental Stages ◽  
Incubation Temperature ◽  
Primordial Germ Cell ◽  
Piaractus Mesopotamicus

scholarly journals Not All H3K4 Methylations Are Created Equal: Mll2/COMPASS Dependency in Primordial Germ Cell Specification

2017 ◽  
Vol 65 (3) ◽  
pp. 460-475.e6 ◽  
Author(s):  
Deqing Hu ◽  
Xin Gao ◽  
Kaixiang Cao ◽  
Marc A. Morgan ◽  
Gloria Mas ◽  
...  
Keyword(s):  
Germ Cell ◽  
Primordial Germ Cell ◽  
Cell Specification ◽  
Germ Cell Specification

scholarly journals Heavily Armed Ancestors: CRISPR Immunity and Applications in Archaea with a Comparative Analysis of CRISPR Types in Sulfolobales

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1523
Author(s):  
Isabelle Anna Zink ◽  
Erika Wimmer ◽  
Christa Schleper
Keyword(s):  
Comparative Analysis ◽  
Molecular Mechanisms ◽  
Model Organisms ◽  
Special Focus ◽  
Natural Environments ◽  
Type I ◽  
Accessory Proteins ◽  
Type Iii

Prokaryotes are constantly coping with attacks by viruses in their natural environments and therefore have evolved an impressive array of defense systems. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is an adaptive immune system found in the majority of archaea and about half of bacteria which stores pieces of infecting viral DNA as spacers in genomic CRISPR arrays to reuse them for specific virus destruction upon a second wave of infection. In detail, small CRISPR RNAs (crRNAs) are transcribed from CRISPR arrays and incorporated into type-specific CRISPR effector complexes which further degrade foreign nucleic acids complementary to the crRNA. This review gives an overview of CRISPR immunity to newcomers in the field and an update on CRISPR literature in archaea by comparing the functional mechanisms and abundances of the diverse CRISPR types. A bigger fraction is dedicated to the versatile and prevalent CRISPR type III systems, as tremendous progress has been made recently using archaeal models in discerning the controlled molecular mechanisms of their unique tripartite mode of action including RNA interference, DNA interference and the unique cyclic-oligoadenylate signaling that induces promiscuous RNA shredding by CARF-domain ribonucleases. The second half of the review spotlights CRISPR in archaea outlining seminal in vivo and in vitro studies in model organisms of the euryarchaeal and crenarchaeal phyla, including the application of CRISPR-Cas for genome editing and gene silencing. In the last section, a special focus is laid on members of the crenarchaeal hyperthermophilic order Sulfolobales by presenting a thorough comparative analysis about the distribution and abundance of CRISPR-Cas systems, including arrays and spacers as well as CRISPR-accessory proteins in all 53 genomes available to date. Interestingly, we find that CRISPR type III and the DNA-degrading CRISPR type I complexes co-exist in more than two thirds of these genomes. Furthermore, we identified ring nuclease candidates in all but two genomes and found that they generally co-exist with the above-mentioned CARF domain ribonucleases Csx1/Csm6. These observations, together with published literature allowed us to draft a working model of how CRISPR-Cas systems and accessory proteins cross talk to establish native CRISPR anti-virus immunity in a Sulfolobales cell.

Sall4 Is Essential for Mouse Primordial Germ Cell Specification by Suppressing Somatic Cell Program Genes

Stem Cells ◽  
2014 ◽  
Vol 33 (1) ◽  
pp. 289-300 ◽  
Author(s):  
Yasuka L. Yamaguchi ◽  
Satomi S. Tanaka ◽  
Maho Kumagai ◽  
Yuka Fujimoto ◽  
Takeshi Terabayashi ◽  
...  
Keyword(s):  
Germ Cell ◽  
Somatic Cell ◽  
Primordial Germ Cell ◽  
Cell Specification ◽  
Germ Cell Specification ◽  
Mouse Primordial Germ Cell

scholarly journals The novel ciliogenesis regulator DYRK2 governs Hedgehog signaling during mouse embryogenesis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Saishu Yoshida ◽  
Katsuhiko Aoki ◽  
Ken Fujiwara ◽  
Takashi Nakakura ◽  
Akira Kawamura ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
The Novel ◽  
Mammalian Development ◽  
Hh Signaling ◽  
Functional Analyses ◽  
First Time ◽  
Insight Into

Mammalian Hedgehog (Hh) signaling plays key roles in embryogenesis and uniquely requires primary cilia. Functional analyses of several ciliogenesis-related genes led to the discovery of the developmental diseases known as ciliopathies. Hence, identification of mammalian factors that regulate ciliogenesis can provide insight into the molecular mechanisms of embryogenesis and ciliopathy. Here, we demonstrate that DYRK2 acts as a novel mammalian ciliogenesis-related protein kinase. Loss of Dyrk2 in mice causes suppression of Hh signaling and results in skeletal abnormalities during in vivo embryogenesis. Deletion of Dyrk2 induces abnormal ciliary morphology and trafficking of Hh pathway components. Mechanistically, transcriptome analyses demonstrate down-regulation of Aurka and other disassembly genes following Dyrk2 deletion. Taken together, the present study demonstrates for the first time that DYRK2 controls ciliogenesis and is necessary for Hh signaling during mammalian development.

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