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First published online November 7, 2008
doi: 10.1242/10.1242/dev.022434

Development 135, 3817-3827 (2008)
Published by The Company of Biologists 2008
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Less is more: specification of the germline by transcriptional repression

Akira Nakamura1 and Geraldine Seydoux2

1 Laboratory for Germline Development, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
2 Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.


Figure 1
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  		Fig. 1. Early germ cell development in Drosophila, C. elegans and mice. (A,B) Anterior is towards the left. (A) In C. elegans, the germ plasm (pink) becomes asymmetric in the zygote and segregates specifically to the germline blastomeres P1-P4. Z2 and Z3, the daughters of P4, become the primordial germ cells (PGCs), and move inside the embryo in close association with intestinal cells (yellow). Later they are joined by Z1 and Z4, the founder cells of the somatic gonad. (B) Drosophila: germ plasm (pink) is assembled during oogenesis and preformed in the posterior pole region of eggs. Pole cells incorporate germ plasm, and are carried inside the embryo during germ band extension, pass through the midgut epithelia (yellow) into the hemocoel, migrate toward mesoderm (green), and then coalesce with somatic gonadal cells to form the embryonic gonads. (C) The anterior-posterior axis of mouse embryos is established by the anterior visceral endoderm (AVE). During embryonic day (E) 6.25-6.5, extra-embryonic signals promote four to eight proximal epiblast cells to activate Blimp1 expression (pink). These cells migrate to an extra-embryonic location and by E7.25, have proliferated to form ~40 alkaline phosphatase (AP)-positive PGCs that are present at the root of the allantois. These PGCs migrate back into the embryo in association with the hindgut (yellow) to eventually colonize the genital ridges (somatic gonad).

 

Figure 2
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  		Fig. 2. mRNA transcription and its repression during germ cell specification. (A) Steps of RNA transcription. (a) Initiation: the pre-initiation complex [consisting of RNAPII (blue) and the general transcriptional factors (GTFs, pink)] assembles at the promoter. (b) Promoter clearance: Cdk7 (orange) in the TFIIH complex phosphorylates Ser5 in the CTD repeats (green circles), allowing the polymerase to clear the promoter and recruit capping enzymes. (c) 5' capping and pausing: shortly after initiation, RNAPII is paused by the action of negative factors [DISF (DRB sensitivity-inducing factor) and NELF (negative elongation factor)]. P-TEFb (positive transcription elongation factor b) phosphorylates CTD Ser2 (green circles), DISF and NELF, promoting the dissociation of NELF and the conversion of DSIF into a positive elongation factor, leading to productive elongation (d). CTD Ser2 phosphorylation also promotes recruitment of mRNA-processing enzymes. (B-D) Repression of mRNA transcription by germline proteins. (B) In one- to two-cell stage C. elegans embryos, maternally loaded OMA-1 and OMA-2 compete with TAF-12 for binding to the GTF TAF-4, keeping it sequestered in the cytoplasm. (C) In the P2-P4 blastomeres, PIE-1 interacts with the Cyclin T subunit of P-TEFb, blocking its interaction with the CTD and Ser2 phosphorylation. PIE-1 also inhibits Ser5 phosphorylation by an unknown mechanism. (D) In Drosophila pole cells, Pgc binds to the Cdk9 subunit of P-TEFb, and prevents P-TEFb recruitment to chromatin (broken gray arrow). The mechanism that blocks Ser5 phosphorylation is not known.

 

Figure 3
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  		Fig. 3. Order of events during PGC specification. Comparison of the timing of different PGC events in C. elegans, Drosophila and mouse. For C. elegans (where PGCs do not migrate significantly), the `migration' period refers to the period from the birth of Z2 and Z3 to hatching. During this time, Z2 and Z3 associate with the somatic gonad. The `gonad' period refers to the period after hatching (L1 stage), when Z2 and Z3 start to proliferate.

 

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