Potential role of miR-29b in modulation of Dnmt3a and Dnmt3b expression in primordial germ cells of female mouse embryos

Specimens from a polyploid biotype of Dugesia lugubris s.l. were used to clarify the role and fate of germ cells during planarian regeneration. These specimens provide a useful karyological marker because embryonic and somatic cells (3n = 12) can be easily distinguished from male (2n = 8) and female (6n = 24) germ cells by their chromosome number. We succeed in demonstrating how primordial germ cells participate in blastema formation and take part in rebuilding somatic tissues. This evidence was obtained by cutting each planarian specimen twice at appropriate levels. The first aimed to induce primordial germ cells to migrate to the wound. The second cut was performed after complete regeneration and aimed to obtain a blastema from a cephalic or caudal area devoid of gonads. A karyological analysis of mitotic cells present in each blastema obtained after the second cut provided evidence that cells, originally belonging to the germ lines, are still present in somatic tissues even months after complete regeneration. The role of primordial germ cells in planarian regeneration was finally discussed in relation to the phenomenon of metaplasia or transdifferentiation.

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Dual role of Ovol2 on the germ cell lineage segregation during gastrulation in mouse embryogenesis

Development ◽

10.1242/dev.200319 ◽

2022 ◽

Author(s):

Yuki Naitou ◽

Go Nagamatsu ◽

Nobuhiko Hamazaki ◽

Kenjiro Shirane ◽

Masafumi Hayashi ◽

...

Keyword(s):

Germ Cells ◽

Splice Variant ◽

Epithelial To Mesenchymal Transition ◽

Functional Relationship ◽

Germ Line ◽

Primordial Germ Cells ◽

Cell Lineage ◽

Animal Kingdom ◽

Mesenchymal Transition

In mammals, primordial germ cells (PGCs), the origin of the germ line, are specified from the epiblast at the posterior region where gastrulation simultaneously occurs, yet the functional relationship between PGC specification and gastrulation remains unclear. Here, we show that Ovol2, a transcription factor conserved across the animal kingdom, balances these major developmental processes by repressing the epithelial-to-mesenchymal transition (EMT) driving gastrulation and the upregulation of genes associated with PGC specification. Ovol2a, a splice variant encoding a repressor domain, directly regulates EMT-related genes and consequently induces re-acquisition of potential pluripotency during PGC specification, whereas Ovol2b, another splice variant missing the repressor domain, directly upregulates genes associated with PGC specification. Taken together, these results elucidate the molecular mechanism underlying allocation of the germ line among epiblast cells differentiating into somatic cells through gastrulation.

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Developmental expression of c-kit, a proto-oncogene encoded by the W locus

Development ◽

10.1242/dev.109.4.911 ◽

1990 ◽

Vol 109 (4) ◽

pp. 911-923 ◽

Cited By ~ 16

Author(s):

A. Orr-Urtreger ◽

A. Avivi ◽

Y. Zimmer ◽

D. Givol ◽

Y. Yarden ◽

...

Keyword(s):

Germ Cells ◽

Receptor Tyrosine Kinase ◽

Germ Line ◽

Primordial Germ Cells ◽

Mouse Embryos ◽

Developmental Expression ◽

Male Germ Line ◽

Polypeptide Growth Factors ◽

Adult Ovary

Developmental expression of the c-kit proto-oncogene, a receptor tyrosine kinase encoded by the W locus, was investigated by in situ hybridization in normal mouse embryos. Early after implantation transcripts were detectable only in the maternal placenta (6 1/2-7 1/2 days p.c.). Subsequently (8 1/2 days p.c.) numerous ectodermal (neural tube, sensory placodes) and endodermal (embryonic gut) derivatives expressed c-kit. Later transcripts were detected also in the blood islands of the yolk sac and in the embryonic liver, the main sites of embryonic hemopoiesis. Around midgestation, transcripts accumulated in the branchial pouches and also in primordial germ cells of the genital ridges. This complex pattern of expression remained characteristic also later in gestation, when c-kit was expressed in highly differentiated structures of the craniofacial area, in presumptive melanoblasts and in the CNS. In the adult ovary, maternal c-kit transcripts were detected. They were present in the oocytes of both immature and mature ovarian follicles, but not in the male germ line, where c-kit expression may be down regulated. Thus, c-kit activity is complex and appears in multiple tissues including those that also display defects in mutations at the W locus where c-kit is encoded. Correlation between W phenotypes and c-kit expression, as well as the regulation of the complex and multiple expression of polypeptide growth factors and receptors, is discussed.

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Functional requirement of gp130-mediated signaling for growth and survival of mouse primordial germ cells in vitro and derivation of embryonic germ (EG) cells

Development ◽

10.1242/dev.122.4.1235 ◽

1996 ◽

Vol 122 (4) ◽

pp. 1235-1242 ◽

Cited By ~ 3

Author(s):

U. Koshimizu ◽

T. Taga ◽

M. Watanabe ◽

M. Saito ◽

Y. Shirayoshi ◽

...

Keyword(s):

Germ Cells ◽

Intracellular Signaling ◽

Primordial Germ Cells ◽

Cell Formation ◽

Embryonic Stem ◽

Oncostatin M ◽

Receptor Complexes ◽

Binding Subunit

Leukemia inhibitory factor (LIF) is a cytokine known to influence proliferation and/or survival of mouse primordial germ cells (PGC) in culture. The receptor complex for LIF comprises LIF-binding subunit and non-binding signal transducer, gp130. The gp130 was originally identified as a signal-transducing subunit of interleukin (IL)-6 and later also found to be a functional component of receptor complexes for other LIF-related cytokines (oncostatin M [OSM], ciliary neurotrophic factor [CNTF] and IL-11). In this study, we have analyzed the functional role of gp130-mediated signaling in PGC growth in vitro. OSM was able to fully substitute for LIF; both cytokines promoted the proliferation of migratory PGC (mPGC) and enhanced the viability of postmigratory (colonizing) PGC (cPGC) when cultured on SI/SI4-m220 cells. Interestingly, IL-11 stimulated mPGC growth comparable to LIF and OSM, but did not affect cPGC survival. IL-6 and CNTF did not affect PGC. In addition, a combination of IL-6 and soluble IL-6 binding subunit (sIL-6R), which is known to activate intracellular signaling via gp130, fully reproduced the LIF action of PGC. Both in the presence and absence of LIF, addition of neutralizing antibody against gp130 in culture remarkably blocked cPGC survival. These results suggest a pivotal role of gp130 in PGC development, especially that it is indispensable for cPGC survival as comparable to the c-KIT-mediated action. We have further demonstrated that a combination of LIF with forskolin or retinoic acid, a potent mitogen for PGC, supported the proliferation of PGC, leading to propagation of the embryonic stem cell-like cells, termed embryonic germ (EG) cells. Since EG cells were also obtained by using OSM or the IL-6/sIL-6R complex in place of LIF, a significant contribution of gp130-mediated signaling in EG cell formation was further suggested.

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Effects of ten–eleven translocation 1 (Tet1) on DNA methylation and gene expression in chicken primordial germ cells

Reproduction Fertility and Development ◽

10.1071/rd18145 ◽

2019 ◽

Vol 31 (3) ◽

pp. 509 ◽

Cited By ~ 1

Author(s):

Minli Yu ◽

Dongfeng Li ◽

Wanyan Cao ◽

Xiaolu Chen ◽

Wenxing Du

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Germ Cells ◽

Dna Methyltransferase ◽

Primordial Germ Cells ◽

Dna Demethylation ◽

Caveolin 1 ◽

Expression Of Genes ◽

Deleted In Azoospermia

Ten–eleven translocation 1 (Tet1) is involved in DNA demethylation in primordial germ cells (PGCs); however, the precise regulatory mechanism remains unclear. In the present study the dynamics of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in developing PGCs and the role of Tet1 in PGC demethylation were analysed. Results show that 5mC levels dropped significantly after embryonic Day 4 (E4) and 5hmC levels increased reaching a peak at E5–E5.5. Interestingly, TET1 protein was highly expressed during E5 to E5.5, which showed a consistent trend with 5hmC. The expression of pluripotency-associated genes (Nanog, PouV and SRY-box 2 (Sox2)) and germ cell-specific genes (caveolin 1 (Cav1), piwi-like RNA-mediated gene silencing 1 (Piwi1) and deleted in azoospermia-like (Dazl)) was upregulated after E5, whereas the expression of genes from the DNA methyltransferase family was decreased. Moreover, the Dazl gene was highly methylated in early PGCs and then gradually hypomethylated. Knockdown of Tet1 showed impaired survival and proliferation of PGCs, as well as increased 5mC levels and reduced 5hmC levels. Further analysis showed that knockdown of Tet1 led to elevated DNA methylation levels of Dazl and downregulated gene expression including Dazl. Thus, this study reveals the dynamic epigenetic reprogramming of chicken PGCs invivo and the molecular mechanism of Tet1 in regulating genomic DNA demethylation and hypomethylation of Dazl during PGC development.

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Role of stem cell factor in somatic–germ cell interactions during prenatal oogenesis

Zygote ◽

10.1017/s0967199400003373 ◽

1996 ◽

Vol 4 (04) ◽

pp. 349-351 ◽

Cited By ~ 6

Author(s):

Massimo De Felici ◽

Anna Di Carlo ◽

Maurizio Pesce

Keyword(s):

Stem Cell ◽

Germ Cells ◽

Stem Cell Factor ◽

Molecular Mechanisms ◽

Primordial Germ Cells ◽

Significant Progress ◽

Proliferation And Differentiation ◽

Complex Events ◽

Mechanisms Of Migration

During embryogenesis germ cells originate from primordial germ cells (PGCs). The development of mammalian PGCs involves a number of complex events (formation and segregation of PGC precursors, PGC migration and proliferation) which lead to the differentiation of oocytes or prospermatogonia (for a review see De Feliciet al., 1992). During recent years developments in methods for isolation, purification and culture of mouse PGCs have led to significant progress in the understanding of molecular mechanisms of migration, proliferation and differentiation of these cells (for reviews see De Felici, 1994; and De Felici & Pesce, 1994a). In this paper we describe the key role played by stem cell factor (SCF) in PGC development and early folliculogenesis.

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Small non-coding RNA profiling and the role of piRNA pathway genes in the protection of chicken primordial germ cells

BMC Genomics ◽

10.1186/1471-2164-15-757 ◽

2014 ◽

Vol 15 (1) ◽

pp. 757 ◽

Cited By ~ 16

Author(s):

Deivendran Rengaraj ◽

Sang Lee ◽

Tae Park ◽

Hong Lee ◽

Young Kim ◽

...

Keyword(s):

Germ Cells ◽

Primordial Germ Cells ◽

Rna Profiling ◽

Non Coding Rna ◽

Pirna Pathway

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Distribution and space-time relationship of proteoglycans in the extracellular matrix of the migratory pathway of primordial germ cells in mouse embryos

Tissue and Cell ◽

10.1054/tice.1999.0041 ◽

1999 ◽

Vol 31 (3) ◽

pp. 291-300 ◽

Cited By ~ 4

Author(s):

M. Soto-Suazo ◽

P.A. Abrahamsohn ◽

J. Pereda ◽

T.M.T. Zorn

Keyword(s):

Extracellular Matrix ◽

Germ Cells ◽

Primordial Germ Cells ◽

Space Time ◽

Mouse Embryos ◽

Time Relationship ◽

Relationship Of ◽

Migratory Pathway

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NUP50 is necessary for the survival of primordial germ cells in mouse embryos

Reproduction ◽

10.1530/rep-14-0649 ◽

2016 ◽

Vol 151 (1) ◽

pp. 51-58 ◽

Cited By ~ 5

Author(s):

Eunsook Park ◽

Bobae Lee ◽

Bruce E Clurman ◽

Keesook Lee

Keyword(s):

Embryonic Development ◽

Germ Cells ◽

Nuclear Pore Complex ◽

Essential Role ◽

Primordial Germ Cells ◽

Mouse Embryos ◽

Nuclear Pore ◽

Progressive Loss ◽

And Function ◽

Deficient Mice

Nucleoporin 50 kDa (NUP50), a component of the nuclear pore complex, is highly expressed in male germ cells, but its role in germ cells is largely unknown. In this study, we analyzed the expression and function of NUP50 during the embryonic development of germ cells using NUP50-deficient mice. NUP50 was expressed in germ cells of both sexes at embryonic day 15.5 (E15.5), E13.5, and E12.5. In addition, NUP50 expression was also detected in primordial germ cells (PGCs) migrating into the genital ridges at E9.5. The gonads of Nup50−/− embryos of both sexes contained few PGCs at both E11.5 and E12.5 and no developing germ cells at E15.5. The migratory PGCs in Nup50−/− embryos at E9.5 showed increased apoptosis but a normal rate of proliferation, resulting in the progressive loss of germ cells at later stages. Taken together, these results suggest that NUP50 plays an essential role in the survival of PGCs during embryonic development.

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The Central Role of Cadherins in Gonad Development, Reproduction and Fertility

10.20944/preprints202010.0037.v1 ◽

2020 ◽

Author(s):

Rafał P. Piprek ◽

Malgorzata Kloc ◽

Paulina Mizia ◽

Jacek Z. KUBIAK

Keyword(s):

Germ Cells ◽

Reproductive Tract ◽

Primordial Germ Cells ◽

Somatic Cells ◽

Gonad Development ◽

Female Reproductive Tract ◽

Future Research ◽

Corpora Lutea ◽

Germline Development

Cadherins are a group of membrane proteins responsible for cell adhesion. They are crucial for cell sorting and recognition during the morphogenesis, but also play many other roles such as assuring tissue integrity and resistance to stretching, mechanotransduction, cell signaling, regulation of cell proliferation, apoptosis, survival, carcinogenesis, etc. Within the cadherin superfamily, the E- and N-cadherin have been especially well studied. They are involved in many aspects of sexual development and reproduction, such as germline development and gametogenesis, gonad development and functioning, and fertilization. E-cadherin is expressed in the primordial germ cells, (PGCs) and also participates in PGC migration to the developing gonads where they become enclosed by the N-cadherin-expressing somatic cells. The differential expression of cadherins is also responsible for the establishment of the testis or ovary structure. In the adult testes, the N-cadherin is responsible for the integrity of the seminiferous epithelium, regulation of sperm production, and the establishment of the blood-testis barrier. Sex hormones regulate the expression and turnover of N-cadherin influencing the course of spermatogenesis. In the adult ovaries, E- and N-cadherin assure the integrity of ovarian follicles and the formation of corpora lutea. Cadherins are expressed in the mature gametes, and facilitate the capacitation of sperm in the female reproductive tract, and gamete contact during fertilization. The germ cells and accompanying somatic cells express a series of different cadherins, however, their role in gonads and reproduction is still unknown. In this review, we show what is known and unknown about the role of cadherins in the germline and gonad development, and suggest the topics for future research.

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