Primordial Germ Cell Development: Difference between revisions

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[[File:Stage9 bf2-primordial germ cell region.jpg|thumb|alt=Primordial Germ Cell|Human embryo primordial germ cell region ([[Carnegie stage 9]])]]
[[File:Stage9 bf2-primordial germ cell region.jpg|thumb|alt=Primordial Germ Cell|Human embryo primordial germ cell region ([[Carnegie stage 9]])]]
[[File:Chicken-_PGC_grown_in_vitro_02.jpg|thumb|Primordial Germ Cell (chicken) scanning electron micrograph.<ref name="PMID20886037"><pubmed>20886037</pubmed>| [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012968 PLoS One.]</ref>]]
[[File:Chicken-_PGC_grown_in_vitro_02.jpg|thumb|Primordial Germ Cell (chicken) scanning electron micrograph.<ref name="PMID20886037"><pubmed>20886037</pubmed>| [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012968 PLoS One.]</ref>]]
[[File:Mouse- E7.5 late bud 01.jpg|thumb|Labeled mouse primordial germ cells (E7.5)<ref name="PMID19997484"><pubmed>19997484</pubmed>| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777314 PMC2777314] | [http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000756 PLoS Genet.]</ref>]]
[[File:Primordial germ cell 003 icon.jpg|thumb|Labeled mouse primordial germ cells (E10.5) See [[#Mouse Migration Movies|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.
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.


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===Mouse Migration Movies===
===Mouse Migration Movies===
[[File:Mouse- E7.5 late bud 01.jpg|400px]]
Labeled mouse primordial germ cells (E7.5)<ref name="PMID19997484"><pubmed>19997484</pubmed>| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777314 PMC2777314] | [http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000756 PLoS Genet.]</ref>
[[File:Primordial germ cell 003 icon.jpg|400px]]
Labeled mouse primordial germ cells (E10.5) See [[#Mouse Migration Movies|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.
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.

Revision as of 11:10, 21 May 2016

Embryology - 29 Mar 2024    Facebook link Pinterest link Twitter link  Expand to Translate  
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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: genital | Lecture - Medicine | Lecture - Science | Lecture Movie | Medicine - Practical | primordial germ cell | meiosis | endocrine gonad‎ | Genital Movies | genital abnormalities | Assisted Reproductive Technology | puberty | Category:Genital
Female | X | X inactivation | ovary | corpus luteum | oocyte | uterus | vagina | reproductive cycles | menstrual cycle | Category:Female
Male | Y | SRY | testis | spermatozoa | ductus deferens | penis | prostate | Category:Male
Historic Embryology - Genital 
General: 1901 Urinogenital Tract | 1902 The Uro-Genital System | 1904 Ovary and Testis | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1921 Urogenital Development | 1921 External Genital | 1942 Sex Cords | 1953 Germ Cells | Historic Embryology Papers | Historic Disclaimer
Female: 1904 Ovary and Testis | 1904 Hymen | 1912 Urinogenital Organ Development | 1914 External Genitalia | 1914 Female | 1921 External Genital | 1927 Female Foetus 15 cm | 1927 Vagina | 1932 Postnatal Ovary
Male: 1887-88 Testis | 1904 Ovary and Testis | 1904 Leydig Cells | 1906 Testis vascular | 1909 Prostate | 1912 Prostate | 1914 External Genitalia | 1915 Cowper’s and Bartholin’s Glands | 1920 Wolffian tubules | 1935 Prepuce | 1935 Wolffian Duct | 1942 Sex Cords | 1943 Testes Descent | Historic Embryology Papers | 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
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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

Cell Structure

The images below are scanning electron micrographs of the surface of a chicken primordial germ cell that has been grown in culture.[9]

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[10]

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.[11]

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[12]
  • 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.[13]


PGC Markers: alkaline phosphatase-positive, Oct4 (POU5F1), Fragilis (IFITM1)[14], 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.[15]
  • 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.[16]


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 [17]).

  • 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. <pubmed>20886037</pubmed>| PLoS One.
  2. <pubmed>26674564</pubmed>
  3. 3.0 3.1 <pubmed>25263278</pubmed>
  4. <pubmed>20845430</pubmed>
  5. <pubmed>19468308 </pubmed>
  6. <pubmed>19279135</pubmed>
  7. <pubmed> 20027186</pubmed>| Nature Reviews Molecular Cell Biology
  8. <pubmed>19997484</pubmed>| PMC2777314 | PLoS Genet.
  9. <pubmed>20886037</pubmed>| PLoS One.
  10. <pubmed>21886830</pubmed>| PLoS One.
  11. <pubmed>17676999</pubmed>| PMC1950944 | PLoS Genet.
  12. <pubmed>19468308</pubmed>| PLoS One.
  13. <pubmed>20940145</pubmed>
  14. <pubmed>12659663</pubmed>
  15. <pubmed>19906868</pubmed>
  16. <pubmed>20236475</pubmed>
  17. <pubmed>15653597</pubmed>


Reviews

<pubmed>20371640</pubmed>| Reproduction <pubmed>20027186</pubmed> <pubmed>19875497</pubmed> <pubmed>19442193</pubmed> <pubmed>17446386</pubmed> <pubmed>15666347</pubmed> <pubmed>11565804</pubmed> <pubmed>11061420</pubmed>

Articles

<pubmed>19578360</pubmed> <pubmed>18953407</pubmed>


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. (2024, March 29) Embryology Primordial Germ Cell Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Primordial_Germ_Cell_Development

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