Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 Nov;5(11):1078-83.
doi: 10.1038/sj.embor.7400279.

Oct4 is required for primordial germ cell survival

James Kehler  1 , Elena Tolkunova, Birgit Koschorz, Maurizio Pesce, Luca Gentile, Michele Boiani, Hilda Lomelí, Andras Nagy, K John McLaughlin, Hans R Schöler, Alexey Tomilin
Affiliations

Oct4 is required for primordial germ cell survival

James Kehler et al. EMBO Rep. 2004 Nov.

Abstract

Previous studies have shown that Oct4 has an essential role in maintaining pluripotency of cells of the inner cell mass (ICM) and embryonic stem cells. However, Oct4 null homozygous embryos die around the time of implantation, thus precluding further analysis of gene function during development. We have used the conditional Cre/loxP gene targeting strategy to assess Oct4 function in primordial germ cells (PGCs). Loss of Oct4 function leads to apoptosis of PGCs rather than to differentiation into a trophectodermal lineage, as has been described for Oct4-deficient ICM cells. These new results suggest a previously unknown function of Oct4 in maintaining viability of mammalian germline.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Oct4 phenotype in adult gonads. Immunostaining with Oct-4 antibody (C,D,K,L) and haematoxylin and eosin (A,B,E–J,M) of ovaries of indicated ages (A–H) and 10-week-old testes (I–M), isolated from Δ/Δ (A,C,E,G,I,K,M) and the control group Δ/+ (B,D,F,H,J,L) mice, is shown. The arrows and arrowheads point to primordial (arrows) and growing (arrowheads) follicles in the ovarian sections. In the testicular sections, representative germ-cell-deficient seminiferous tubules are labelled as Δ/Δ and those harbouring normal spermatogenic cells of all stages as Δ/+; the arrowheads point to Oct4-positive spermatogonia type B. Shown are mildly (70%; I,K) and severely (100% of germ-cell-free tubules; M) affected testes. Scale bars in (A) for (A,B,E–M) and in (C) for (C,D) represent 100 μm.
Figure 2
Figure 2
Oct4 phenotype in PGCs. Alkaline phosphatase (AP) staining of Δ/Δ (A,C,E,G,I) and Δ/+ embryos (B,D,F,H,J) is shown. The 8.5 dpc (C,D) and 9.5 dpc (E,F) embryos in both groups show no difference in the number of PGCs (arrows) that are located at the base of allantois within the hindgut pocket (8.5 dpc) and, subsequently, in the hindgut endoderm (9.5 dpc). As opposed to the further increase in the number of PGCs in 10.5 dpc Δ/+ embryos (B,H), the Δ/Δ littermates show a marked decrease in the number of PGCs (A,G), which is further apparent in 12.5 dpc genital ridges (I versus J). Photographs were taken from the ventral (C,D,G,H) or lateral (A,B,E,F) sides of embryos. Scale bars in (C) for (C,D) and in (E) for (E,F) represent 100 μm, and scale bar in (I) for (I,J) represents 200 μm.
Figure 3
Figure 3
Apoptosis of Oct4-deficient PGCs. Labelling with Oct-4 antibody (A,B), and double TUNEL (green)/SSEA-1 antibody (red) staining (C,D) of the Δ/Δ (A,C) and control Δ/+ (B,D) 10.5 dpc embryo sections are shown. Significant reduction in Oct4 protein staining can be seen in the Δ/Δ sections. Shown in (C,D) is the AGM region of the same embryos as in Fig 2G,H. Note a strong TUNEL signal in the nuclei of the same clustered cells showing residual SSEA-1 staining on the cell membrane (C and inset). The SSEA-1 signal was notably weaker than that from viable PGCs of the +/Δ embryos (D) yet sufficiently strong to be distinguished from the background. Scale bars in (A) for (A,B) and in (C) for (C,D) represent 50 μm. The inset is a twofold magnification of the PGC/apoptotic area in (C). Arrowhead, PGC; da, dorsal aorta; dm, dorsal mesentery; gr, genital ridge.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anderson R, Copeland TK, Schöler H, Heasman J, Wylie C (2000) The onset of germ cell migration in the mouse embryo. Mech Dev 91: 61–68 - PubMed
    1. De Miguel MP, Cheng L, Holland EC, Federspiel MJ, Donovan PJ (2002) Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral mediated gene transfer. Proc Natl Acad Sci USA 99: 10458–10463 - PMC - PubMed
    1. Donovan PJ, de Miguel MP (2003) Turning germ cells into stem cells. Curr Opin Genet Dev 13: 463–471 - PubMed
    1. Ginsburg M, Snow MH, McLaren A (1990) Primordial germ cells in the mouse embryo during gastrulation. Development 110: 521–528 - PubMed
    1. Gomperts M, Garcia-Castro M, Wylie C, Heasman J (1994) Interactions between primordial germ cells play a role in their migration in mouse embryos. Development 120: 135–141 - PubMed

Publication types

MeSH terms