Steel factor controls midline cell death of primordial germ cells and is essential for their normal 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.

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Proliferation and migration of primordial germ cells in We/We mouse embryos

Developmental Dynamics ◽

10.1002/aja.1001980304 ◽

1993 ◽

Vol 198 (3) ◽

pp. 182-189 ◽

Cited By ~ 119

Author(s):

Mia Buehr ◽

Anne McLaren ◽

Aine Bartley ◽

Susan Darling

Keyword(s):

Germ Cells ◽

Primordial Germ Cells ◽

Mouse Embryos ◽

And Migration ◽

Proliferation And Migration

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DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells

Nature Communications ◽

10.1038/s41467-021-22622-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Lama Tarayrah-Ibraheim ◽

Elital Chass Maurice ◽

Guy Hadary ◽

Sharon Ben-Hur ◽

Alina Kolpakova ◽

...

Keyword(s):

Dna Damage ◽

Cell Death ◽

Germ Cells ◽

Nuclear Translocation ◽

Primordial Germ Cells ◽

Nuclear Accumulation ◽

Dependent Manner ◽

Dnase Ii ◽

Cell Death Pathway ◽

Parp 1

AbstractDuring Drosophila embryonic development, cell death eliminates 30% of the primordial germ cells (PGCs). Inhibiting apoptosis does not prevent PGC death, suggesting a divergence from the conventional apoptotic program. Here, we demonstrate that PGCs normally activate an intrinsic alternative cell death (ACD) pathway mediated by DNase II release from lysosomes, leading to nuclear translocation and subsequent DNA double-strand breaks (DSBs). DSBs activate the DNA damage-sensing enzyme, Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) and the ATR/Chk1 branch of the DNA damage response. PARP-1 and DNase II engage in a positive feedback amplification loop mediated by the release of PAR polymers from the nucleus and the nuclear accumulation of DNase II in an AIF- and CypA-dependent manner, ultimately resulting in PGC death. Given the anatomical and molecular similarities with an ACD pathway called parthanatos, these findings reveal a parthanatos-like cell death pathway active during Drosophila development.

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The role of sphingomyelin and sphingomyelin synthases in cell death, proliferation and migration—from cell and animal models to human disorders

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ◽

10.1016/j.bbalip.2013.12.003 ◽

2014 ◽

Vol 1841 (5) ◽

pp. 692-703 ◽

Cited By ~ 82

Author(s):

Makoto Taniguchi ◽

Toshiro Okazaki

Keyword(s):

Cell Death ◽

Animal Models ◽

Human Disorders ◽

And Migration ◽

Proliferation And Migration

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Memoirs: The Origin and Migration of the Primordial Germ-cells of Sphenodon punctatus

Journal of Cell Science ◽

10.1242/jcs.s2-75.298.251 ◽

1932 ◽

Vol s2-75 (298) ◽

pp. 251-282

Author(s):

MARGARET TRIBE ◽

F.W. ROGERS BRAMBELL

Keyword(s):

Germ Cells ◽

Early Stage ◽

Venous Blood ◽

Primordial Germ Cells ◽

Blood Stream ◽

Yolk Sac ◽

Amoeboid Movement ◽

Stage Of Development ◽

Sphenodon Punctatus ◽

And Migration

1. The primordial germ-cells of Sphenodon originate in the yolk-sac endoderm of the area opaca all round the embiyo, but chiefly in a crescentic area in front of it. 2. They differentiate first at a very early stage of development before the differentiation of the medullary plate. 3. The primordial germ-cells are characterized by their very large size, in comparison with all the other embryonal cells, and by their content of small yolk-spherules which are sub-equal in size. 4. The primordial germ-cells migrate through the yolk-sac endoderm and mesoderm, apparently by their own power of amoeboid movement. Many of them enter the blood-islands and the sinus terminalis. 5. The primordial germ-cells enter the embryo either (1) passively in the venous blood-stream, or (2) actively by migration through the extra-embryonal endoderm and splanchnic mesoderm into the lateral walls and the mesentery of the midgut groove. 6. The primordial germ-cells in the circulation reach the neighbourhood of the germinal ridges in the dorsal aorta or its branches. They then penetrate the walls of the vessels and migrate through the intervening tissues, together with those that have reached the base of the mid-gut mesentery by way of the splanchnic mesoderm and the mid-gut wall, to the germinal ridges. 7. Many primordial germ-cells get lost during their migration. This is especially true of those travelling in the blood-stream. Such aberrant primordial germ-cells are found occasionally in almost any part of the embryo,, but occur most often in the head, especially in the region of the fore-brain. They ultimately disappear. 8. The primordial germ-cells enter the forming germinal ridges before the coelomic epithelium covering them has begun to proliferate. 9. The primordial germ-cells, having reached the germinal ridges, lose their characteristic yolk-content and enter on the prophase of the heterotypic division.

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Proliferation and migration of primordial germ cells during compensatory growth in mouse embryos

Development ◽

10.1242/dev.64.1.133 ◽

1981 ◽

Vol 64 (1) ◽

pp. 133-147

Author(s):

P. P. L. Tam ◽

M. H. L. Snow

Keyword(s):

Mitomycin C ◽

Germ Cells ◽

Compensatory Growth ◽

Primordial Germ Cells ◽

Primordial Germ Cell ◽

Primitive Streak ◽

Mouse Embryos ◽

Newborn Mice ◽

Embryonic Life ◽

And Migration

Primitive-streak-stage mouse embryos were treated with Mitomycin C injected intraperitoneally into pregnant females at 6·75–7·0 days post coitum. The newborn mice developed poorly and mortality was high during the suckling period. Many weaned survivors showed impaired fertility and poor breeding performance. Histological examination revealed a paucity of germ cells in the adult gonads. The deficiency was mainly caused by a severe reduction of the primordial germ cell population in early embryonic life, which was not fully compensated for during the compensatory growth phase of the Mitomycin C-treated embryo. Also contributing to such impaired fertility were retarded migration of the primordial germ cells into the genital ridges, poor development of the foetal gonad and secondary loss of the germ cells during gametogenesis in males.

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Inter-species transplantation and migration of primordial germ cells in cyprinid fish

The International Journal of Developmental Biology ◽

10.1387/ijdb.103111ts ◽

2010 ◽

Vol 54 (10) ◽

pp. 1479-1484 ◽

Cited By ~ 29

Author(s):

Taiju Saito ◽

Rie Goto-Kazeto ◽

Takafumi Fujimoto ◽

Yutaka Kawakami ◽

Katsutoshi Arai ◽

...

Keyword(s):

Germ Cells ◽

Primordial Germ Cells ◽

Cyprinid Fish ◽

And Migration

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Embryonic Exposure to Bisphenol A Impairs Primordial Germ Cell Migration without Jeopardizing Male Breeding Capacity

Biomolecules ◽

10.3390/biom9080307 ◽

2019 ◽

Vol 9 (8) ◽

pp. 307 ◽

Cited By ~ 5

Author(s):

Marta Lombó ◽

Lidia Getino-Álvarez ◽

Alexandra Depincé ◽

Catherine Labbé ◽

María Herráez

Keyword(s):

Bisphenol A ◽

Hormone Receptors ◽

Primordial Germ Cells ◽

Primordial Germ Cell ◽

Morphometric Study ◽

Embryonic Exposure ◽

Germ Cell Migration ◽

Embryonic Life ◽

And Migration ◽

Proliferation And Migration

A large amount of chemicals are released to the environment each year. Among them, bisphenol A (BPA) is of utmost concern since it interferes with the reproductive system of wild organisms due to its capacity to bind to hormone receptors. Additionally, BPA epigenotoxic activity is known to affect basic processes during embryonic life. However, its effects on primordial germ cells (PGCs) proliferation and migration, both mechanisms being crucial for gametogenesis, remain unknown. To investigate the effects of BPA on PGCs migration and eventual testicle development, zebrafish embryos were exposed to 100, 2000 and 4000 µg/L BPA during the first 24 h of development. Vasa immunostaining of PGCs revealed that exposure to 2000 and 4000 µg/L BPA impaired their migration to the genital ridge. Two pivotal genes of PGCs migration (cxcr4b and sdf1a) were highly dysregulated in embryos exposed to these doses, whereas DNA methylation and epigenetic marks in PGCs and their surrounding somatic cells were not altered. Once embryos reached adulthood, the morphometric study of their gonads revealed that, despite the reduced number of PGCs which colonized the genital ridges, normal testicles were developed. Although H3K9ac decreased in the sperm from treated fishes, it did not affect the progeny development.

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