Primordial Germ Cell Development

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Introduction

Primordial Germ Cell (chicken) scanning electron micrograph.

Labeled mouse primordial germ cells (E7.5)

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: 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

Loss of Lhx1 activity impacts on the localization of primordial germ cells in the mouse "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 "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 "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."

(More? Recent References)

Textbooks

• 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

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.

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.

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 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

X-linked Gene Expression

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

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

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.

PGC Markers: alkaline phosphatase-positive, Oct4 (POU5F1), Fragilis (IFITM1), 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.
• 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.

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 ).

• 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

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, April 24) Embryology Primordial Germ Cell Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Primordial_Germ_Cell_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G