Primordial Germ Cell Development

From Embryology
Embryology - 30 Jul 2016    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Introduction

Primordial Germ Cell
Human embryo primordial germ cell region (Carnegie stage 9)
Primordial Germ Cell (chicken) scanning electron micrograph.[1]

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 | Medicine - Practical | Primordial Germ Cell | Meiosis | Female | Ovary | Oocyte | Uterus | Vagina | Reproductive Cycles | Menstrual Cycle | Male | Testis | Spermatozoa | Prostate | Genital Movies | Abnormalities | Assisted Reproductive Technology | Puberty | Category:Genital
Historic Embryology - Genital 
1902 The Uro-Genital System | 1912 Urinogenital Organ Development | 1921 Urogenital Development | 1921 External Genital Development | 1927 Female Foetus 15 cm | 1943 Testes Descent | Historic Disclaimer

Some Recent Findings

  • Review - Key Signaling Events for Committing Mouse Pluripotent Stem Cells to the Germline Fate[2] "The process of germline development carries genetic information and preparatory totipotency across generations. The last decade has witnessed remarkable successes in the generation of germline cells from mouse pluripotent stem cells, especially induced germline cells with the capacity for producing viable offspring, suggesting clinical applications of induced germline cells in humans. However, to date, the culture systems for germline induction with accurate sex-specific meiosis and epigenetic reprogramming have not been well-established. In this study, we primarily focus on the mouse model to discuss key signaling events for germline induction. We review mechanisms of competent regulators on primordial germ cell induction and discuss current achievements and difficulties in inducing sex-specific germline development. Furthermore, we review the developmental identities of mouse embryonic stem cells and epiblast stem cells under certain defined culture conditions as it relates to the differentiation process of becoming germline cells."
  • Sall4 is Essential for Mouse Primordial Germ Cell Specification by Suppressing Somatic Cell Program Genes[3] "The Sall4 zinc finger protein is a critical transcription factor for pluripotency in embryonic stem cells (ESCs). ...Given that Sall4 and Prdm1 are known to associate with the histone deacetylase repressor complex, our findings suggest that Sall4 suppresses the somatic cell program possibly by recruiting the repressor complex in conjunction with Prdm1; therefore, it is essential for PGC specification."
More recent papers
Mark Hill.jpg
PubMed logo.gif

This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Primordial Germ Cell

Kanako Morohaku, Ren Tanimoto, Keisuke Sasaki, Ryouka Kawahara-Miki, Tomohiro Kono, Katsuhiko Hayashi, Yuji Hirao, Yayoi Obata Complete in vitro generation of fertile oocytes from mouse primordial germ cells. Proc. Natl. Acad. Sci. U.S.A.: 2016; PubMed 27457928

Daniel Nettersheim, Isabell Arndt, Rakesh Sharma, Stefanie Riesenberg, Sina Jostes, Simon Schneider, Michael Hölzel, Glen Kristiansen, Hubert Schorle The cancer/testis-antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas. Br. J. Cancer: 2016; PubMed 27441500

R A-M Kenngott, W Scholz, F Sinowatz Ultrastructural Aspects of the Prenatal Bovine Ovary Differentiation with a Special Focus on the Interstitial Cells. Anat Histol Embryol: 2016; PubMed 27439665

Jingjing Sun, Man-Chun Ting, Mamoru Ishii, Robert Maxson Msx1 and Msx2 function together in the regulation of primordial germ cell migration in the mouse. Dev. Biol.: 2016; PubMed 27435625

Nathalie Oulhen, Gary M Wessel Differential Nanos 2 protein stability results in selective germ cell accumulation in the sea urchin. Dev. Biol.: 2016; PubMed 27424271

Older papers
  • Loss of Lhx1 activity impacts on the localization of primordial germ cells in the mouse[4] "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[5] "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[6] "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[7]

Mouse Migration Movies

Mouse- E7.5 late bud 01.jpg

Labeled mouse primordial germ cells (E7.5)[8]

Primordial germ cell 003 icon.jpg

Labeled mouse primordial germ cells (E10.5) See 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.

Mouse Primordial Germ Cell Migration
Primordial germ cell 001 icon.jpg
 ‎‎Germ Cell E9.0
Page | Play
Primordial germ cell 002 icon.jpg
 ‎‎Germ Cell E9.5
Page | Play
Primordial germ cell 003 icon.jpg
 ‎‎Germ Cell E10.5
Page | Play
Links: Mouse Development

Fetal Ovary Meiosis

Fetal ovary meiosis 02.jpg

Fetal ovary meiosis[9]

Ectopic PGCs

Fetal adrenal ectopic germ cells 01.jpg
Ectopic PGC's in human adrenal gland in first trimester male week 8 (GA week 10) and female week 11 (GA week 13).[9]


  • A B - Germ cells were identified by expression of POU5F1 (red) and/or DDX4 (green)
  • C D - DDX4+ (green) germ cells do not express H2AFX (red), however, many H2AFX+ cells were present in the adrenals (white arrows)
  • E F - DDX4+ (red) germ cells were not TUNEL-positive (green), however, many TUNEL+ cells were present in the adrenals (white arrows)



Cell Structure

The images below are scanning electron micrographs of the surface of a chicken primordial germ cell that has been grown in culture.[10]

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[11]

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.[12]

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[13]
  • Prdm1 and Prdm14 - PR domain proteins expressed in mouse (E6.25), suppresses somatic differentiation.
  • Sall4 - zinc finger protein, inactivation of this transcription factor in mouse can reduce PGC number.[3]

A 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.[14]


PGC Markers: alkaline phosphatase-positive, Oct4 (POU5F1), Fragilis (IFITM1)[15], 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.[16]
  • 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.[17]


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 [18]).

  • 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 PubMed 20886037 | PLoS One.
  2. Jian-Qi Wang, Wen-Guang Cao Key Signaling Events for Committing Mouse Pluripotent Stem Cells to the Germline Fate. Biol. Reprod.: 2015; PubMed 26674564
  3. 3.0 3.1 Yasuka L Yamaguchi, Satomi S Tanaka, Maho Kumagai, Yuka Fujimoto, Takeshi Terabayashi, Yasuhisa Matsui, Ryuichi Nishinakamura Sall4 is Essential for Mouse Primordial Germ Cell Specification by Suppressing Somatic Cell Program Genes. Stem Cells: 2014; PubMed 25263278
  4. 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 PubMed 20845430
  5. 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 PubMed 19468308
  6. 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 PubMed 19279135
  7. 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 PubMed 20027186 | Nature Reviews Molecular Cell Biology
  8. 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 PubMed 19997484 | PMC2777314 | PLoS Genet.
  9. 9.0 9.1 A Marijne Heeren, Nannan He, Aline F de Souza, Angelique Goercharn-Ramlal, Liesbeth van Iperen, Matthias S Roost, Maria M Gomes Fernandes, Lucette A J van der Westerlaken, Susana M Chuva de Sousa Lopes On the development of extragonadal and gonadal human germ cells. Biol Open: 2016; PubMed 26834021 | Biol Open.
  10. 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 PubMed 20886037 | PLoS One.
  11. 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 PubMed 21886830 | PLoS One.
  12. Michihiko Sugimoto, Kuniya Abe X chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genet.: 2007, 3(7);e116 PubMed 17676999 | PMC1950944 | PLoS Genet.
  13. 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 PubMed 19468308 | PLoS One.
  14. 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 PubMed 20940145
  15. 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 PubMed 12659663
  16. 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 PubMed 19906868
  17. Lionel A Sanz, Satya K Kota, Robert Feil Genome-wide DNA demethylation in mammals. Genome Biol.: 2010, 11(3);110 PubMed 20236475
  18. 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: 2005, 25(1);215-42 PubMed 15653597


Reviews

Mitinori Saitou, Masashi Yamaji Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences. Reproduction: 2010, 139(6);931-42 PubMed 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 PubMed 20027186

Yasuhisa Matsui The molecular mechanisms regulating germ cell development and potential. J. Androl.: 2009, 31(1);61-5 PubMed 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 PubMed 19442193

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

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

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

M De Felici Regulation of primordial germ cell development in the mouse. Int. J. Dev. Biol.: 2000, 44(6);575-80 PubMed 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 PubMed 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 PubMed 18953407


Search PubMed

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

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.


Glossary Links

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols



Cite this page: Hill, M.A. (2016) Embryology Primordial Germ Cell Development. Retrieved July 30, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Primordial_Germ_Cell_Development

What Links Here?
© Dr Mark Hill 2016, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G