Primordial Germ Cell Development

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Contents

Introduction

Primordial Germ Cell (chicken) scanning electron micrograph.[1]
Labeled mouse primordial germ cells (E7.5)[2]
Labeled mouse primordial germ cells (E10.5) See Mouse Migration Movies

Early in development at the time of gastrulation a small group of cells are "put aside" to later form oocytes and spermatozoa. This population of cells is described as the primordial germ cells (PGCs). These cells also migrate initially into the posterior endoderm that forms the hindgut and from there into the genital ridge that will be the site of the developing gonad. The maintenance of pluripotency within this cell population may arise through epigenetic modifications that suppress somatic differentiation programs.

This population of cells when transformed is also thought to give rise to testicular germ cell tumours.


Genital Links: Introduction | Lecture - Medicine | Lecture - Science | Online Practical | Primordial Germ Cell | Meiosis | Female | Ovary | Oocyte | Uterus | Vagina | Male | Testis | Spermatozoa | Prostate | Genital Movies | Abnormalities | Assisted Reproductive Technology | Puberty | Category:Genital
Historic Embryology: 1912 Urinogenital Organ Development | 1921 Urogenital Development | 1921 External Genital Development | Historic Disclaimer

Some Recent Findings

  • Loss of Lhx1 activity impacts on the localization of primordial germ cells in the mouse[3] "To dissect the specific role of Lhx1 in germ cell development, we studied embryos with conditional inactivation of Lhx1 activity in epiblast derivatives, which, in contrast to completely null embryos, develop normally through gastrulation before manifesting a head truncation phenotype. Initially, PGCs are localized properly to the definitive endoderm of the posterior gut in the conditional mutant embryos, but they depart from the embryonic gut prematurely. The early exit of PGCs from the gut is accompanied by the failure to maintain a strong expression of Ifitm1 in the mesoderm enveloping the gut, which may mediate the repulsive activity that facilitates the retention of PGCs in the hindgut during early organogenesis. Lhx1 therefore may influence the localization of PGCs by modulating Ifitm1-mediated repulsive activity."
  • Dazl functions in maintenance of pluripotency and genetic and epigenetic programs of differentiation in mouse primordial germ cells in vivo and in vitro[4] "We demonstrate that disruption of Dazl results in a post-migratory, pre-meiotic reduction in PGC number accompanied by aberrant expression of pluripotency genes and failure to erase and re-establish genomic imprints in isolated male and female PGCs, as well as subsequent defect in progression through meiosis. Moreover, the phenotypes observed in vivo were mirrored by those in vitro, with inability of isolated mutant PGCs to establish pluripotent EG (embryonic germ) cell lines and few residual Oct-4-expressing cells remaining after somatic differentiation of mESCs carrying a Dazl null mutation. Finally, we observed that even within undifferentiated mESCs, a nascent germ cell subpopulation exists that was effectively eliminated with ablation of Dazl."
  • Steel factor controls primordial germ cell survival and motility from the time of their specification in the allantois, and provides a continuous niche throughout their migration[5] "Steel factor is an essential survival and proliferation factor for primordial germ cells (PGCs) during their migration in the early mouse embryo. ...These data, together with previously published data, show that PGCs are Steel factor dependent from their initial specification until they colonize the genital ridges, and suggest the existence of a ;spatio-temporal niche' that travels with this important pluripotential cell population in the embryo."

Textbooks

Historic-ovary.jpg Historic-testis.jpg

  • Human Embryology (2nd ed.) Larson Chapter 10 p261-306
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 13 p303-346
  • Before We Are Born (5th ed.) Moore and Persaud Chapter 14 p289-326
  • Essentials of Human Embryology, Larson Chapter 10 p173-205
  • Human Embryology, Fitzgerald and Fitzgerald Chapter 21-22 p134-152
  • Developmental Biology (6th ed.) Gilbert Chapter 14 Intermediate Mesoderm

Primordial Germ Cell Migration

Species Comparison of Migration

Stages of primordial germ cell migration.jpg

Stages of primordial germ cell migration[6]

Mouse Migration Movies

The movies below show labeled primordial germ cells (green) migrating within the mouse embryo between the periods of E9.0 to E10.5 into the genital ridge region that will later form the gonad.

Primordial germ cell 001 icon.jpg Primordial germ cell 002 icon.jpg Primordial germ cell 003 icon.jpg
E9.0 E9.5 E10.5
Quicktime version Quicktime version Quicktime version
Flash version Flash version Flash version

Cell Structure

The images below are scanning electron micrographs of the surface of a chicken primordial germ cell that has been grown in culture.[7]

Chicken- PGC grown in vitro 02.jpg Chicken- PGC grown in vitro 03.jpg

The first image shows the whole cell and the second image shows detail of the cell surface showing extensions.

DNA Methylation

Mouse primordial germ cell DNA methylation[8]

Demethylation

  • Global DNA demethylation occurs in primordial germ cells about the time when they colonize the genital ridges.


Remethylation

  • Male - prospermatogonia methylation occurs during fetal stages.
  • Female - oocytes methylation occurs postnatally.


Links: Molecular Development - Epigenetics
Primordial germ cell DNA methylation 01.jpg

X-linked Gene Expression

Mouse- X-linked gene expression in primordial germ cells.jpg

Mouse- X-linked gene expression during primordial germ cell development.[9]

Each circle graph indicates the ratio of cells that are positive (yellow) and negative (black) for each gene, and biallelically (red) and monoallelically (blue) expressed in cells positive for each gene.


Links: X Inactivation | Mouse Development

Molecular

File:Model of Dazl germ cell function[10]

Study has recently identified 11 genes that are specifically expressed in male and female fetal germ cells, both in vivo and in vitro, but are not expressed in embryonic stem cells.[11]


PGC Markers: alkaline phosphatase-positive, Oct4 (POU5F1), Fragilis (IFITM1)[12], Stella (DPPA3), Dazl, and Vasa (DDX4).

  • Steel factor - (KITLG) a ligand for the KIT tyrosine kinase receptor.
  • DAZL
  • dead end - coding an RNA binding protein mainly expressed in the germ cells of vertebrates.
  • Blimp1 - B-Lymphocyte induced maturation protein-1 (PRDM1)
  • Prmt5 - protein arginine methyltransferase-5
  • Nanog - knockdown induces apoptotic cell death in mouse migrating primordial germ cells.[13]
  • AID - Activation-Induced cytidine Deaminase enzyme required for demethylation (removal of CpG methylation). Within the genome, DNA methylation is associated with epigenetic mechanisms and occurs at cytosine residues that are followed by guanines.[14]


OMIM Links: POU5F1 | DAZL | DPPA3 | IFITM1 | DDX4 | KITLG | PRDM1

Abnormalities

Teratomas

Common group of fetal tumors occuring along the body midline, anywhere from the coccyx to the pineal gland, reflecting the developmental PGC migration pathway (for review see [15]).

  • Histologically classified as either mature or immature.
  • Immature elements consisting principally of primitive neuroglial tissue and neuroepithelial rosettes and have have a generally favorable prognosis.
  • Sacrococcygeal teratomas - most common site (70%–80% of all teratomas).
    • classified into four types based on the amount of mass present externally versus internally.


Testicular germ cell tumours (seminoma)

References

  1. Jin Won Choi, Sujung Kim, Tae Min Kim, Young Min Kim, Hee Won Seo, Tae Sub Park, Jae-Wook Jeong, Gwonhwa Song, Jae Yong Han Basic fibroblast growth factor activates MEK/ERK cell signaling pathway and stimulates the proliferation of chicken primordial germ cells. PLoS ONE: 2010, 5(9);e12968 PMID:20886037 | PLoS One.
  2. Liqin Cao, Hiroshi Shitara, Michihiko Sugimoto, Jun-Ichi Hayashi, Kuniya Abe, Hiromichi Yonekawa New evidence confirms that the mitochondrial bottleneck is generated without reduction of mitochondrial DNA content in early primordial germ cells of mice. PLoS Genet.: 2009, 5(12);e1000756 PMID:19997484 | PMC2777314 | PLoS Genet.
  3. Satomi S Tanaka, Yasuka L Yamaguchi, Kirsten A Steiner, Toru Nakano, Ryuichi Nishinakamura, Kin Ming Kwan, Richard R Behringer, Patrick P L Tam Loss of Lhx1 activity impacts on the localization of primordial germ cells in the mouse. Dev. Dyn.: 2010, 239(11);2851-9 PMID:20845430
  4. Kelly M Haston, Joyce Y Tung, Renee A Reijo Pera Dazl functions in maintenance of pluripotency and genetic and epigenetic programs of differentiation in mouse primordial germ cells in vivo and in vitro. PLoS ONE: 2009, 4(5);e5654 PMID:19468308
  5. Ying Gu, Chris Runyan, Amanda Shoemaker, Azim Surani, Chris Wylie Steel factor controls primordial germ cell survival and motility from the time of their specification in the allantois, and provides a continuous niche throughout their migration. Development: 2009, 136(8);1295-303 PMID:19279135
  6. Brian E Richardson, Ruth Lehmann Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat. Rev. Mol. Cell Biol.: 2010, 11(1);37-49 PMID:20027186 | Nature Reviews Molecular Cell Biology
  7. Jin Won Choi, Sujung Kim, Tae Min Kim, Young Min Kim, Hee Won Seo, Tae Sub Park, Jae-Wook Jeong, Gwonhwa Song, Jae Yong Han Basic fibroblast growth factor activates MEK/ERK cell signaling pathway and stimulates the proliferation of chicken primordial germ cells. PLoS ONE: 2010, 5(9);e12968 PMID:20886037 | PLoS One.
  8. Masanobu Abe, Shirley Y Tsai, Seung-Gi Jin, Gerd P Pfeifer, Piroska E Szabó Sex-specific dynamics of global chromatin changes in fetal mouse germ cells. PLoS ONE: 2011, 6(8);e23848 PMID:21886830 | PLoS One.
  9. Michihiko Sugimoto, Kuniya Abe X chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genet.: 2007, 3(7);e116 PMID:17676999 | PMC1950944 | PLoS Genet.
  10. Kelly M Haston, Joyce Y Tung, Renee A Reijo Pera Dazl functions in maintenance of pluripotency and genetic and epigenetic programs of differentiation in mouse primordial germ cells in vivo and in vitro. PLoS ONE: 2009, 4(5);e5654 PMID:19468308 | PLoS One.
  11. Davood Sabour, Marcos J Araúzo-Bravo, Karin Hübner, Kinarm Ko, Boris Greber, Luca Gentile, Martin Stehling, Hans R Schöler Identification of genes specific to mouse primordial germ cells through dynamic global gene expression. Hum. Mol. Genet.: 2011, 20(1);115-25 PMID:20940145
  12. U C Lange, M Saitou, P S Western, S C Barton, M A Surani The fragilis interferon-inducible gene family of transmembrane proteins is associated with germ cell specification in mice. BMC Dev. Biol.: 2003, 3();1 PMID:12659663
  13. Shinpei Yamaguchi, Kazuki Kurimoto, Yukihiro Yabuta, Hiroyuki Sasaki, Norio Nakatsuji, Mitinori Saitou, Takashi Tada Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. Development: 2009, 136(23);4011-20 PMID:19906868
  14. Lionel A Sanz, Satya K Kota, Robert Feil Genome-wide DNA demethylation in mammals. Genome Biol.: 2010, 11(3);110 PMID:20236475
  15. Paula J Woodward, Roya Sohaey, Anne Kennedy, Kelly K Koeller From the archives of the AFIP: a comprehensive review of fetal tumors with pathologic correlation. Radiographics: , 25(1);215-42 PMID:15653597


Reviews

Mitinori Saitou, Masashi Yamaji Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences. Reproduction: 2010, 139(6);931-42 PMID:20371640 | Reproduction Brian E Richardson, Ruth Lehmann Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat. Rev. Mol. Cell Biol.: 2010, 11(1);37-49 PMID:20027186

Yasuhisa Matsui The molecular mechanisms regulating germ cell development and potential. J. Androl.: , 31(1);61-5 PMID:19875497

Massimo De Felici, Donatella Farini, Susanna Dolci In or out stemness: comparing growth factor signalling in mouse embryonic stem cells and primordial germ cells. Curr Stem Cell Res Ther: 2009, 4(2);87-97 PMID:19442193

Katsuhiko Hayashi, Susana M Chuva de Sousa Lopes, M Azim Surani Germ cell specification in mice. Science: 2007, 316(5823);394-6 PMID:17446386

Yasuhisa Matsui, Daiji Okamura Mechanisms of germ-cell specification in mouse embryos. Bioessays: 2005, 27(2);136-43 PMID:15666347

C M Watson, P P Tam Cell lineage determination in the mouse. Cell Struct. Funct.: 2001, 26(3);123-9 PMID:11565804

M De Felici Regulation of primordial germ cell development in the mouse. Int. J. Dev. Biol.: 2000, 44(6);575-80 PMID:11061420


Articles

Jason A West, Srinivas R Viswanathan, Akiko Yabuuchi, Kerianne Cunniff, Ayumu Takeuchi, In-Hyun Park, Julia E Sero, Hao Zhu, Antonio Perez-Atayde, A Lindsay Frazier, M Azim Surani, George Q Daley A role for Lin28 in primordial germ-cell development and germ-cell malignancy. Nature: 2009, 460(7257);909-13 PMID:19578360

Gabriela Durcova-Hills, Fuchou Tang, Gina Doody, Reuben Tooze, M Azim Surani Reprogramming primordial germ cells into pluripotent stem cells. PLoS ONE: 2008, 3(10);e3531 PMID:18953407


Search PubMed

Search Pubmed: Primordial Germ Cell Migration | Primordial Germ Cell | Testicular germ cell tumours

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Cite this page: Hill, M.A. (2014) Embryology Primordial Germ Cell Development. Retrieved April 24, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=Primordial_Germ_Cell_Development

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Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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