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\b[Germ plasm inheritance places germline-promoting material into selected <biological cells>; induction establishes germline identity through signalling to competent <biological cells>.] Both must protect the future <germline> from inappropriate somatic differentiation. They differ in how that programme begins and in how broadly early <transcription> is repressed. <primordial germ cells> are precursors of future <gametes>, not simply <biological cells> expressing one widely shared germ-cell marker.
In <Drosophila melanogaster>, maternal <oskar messenger RNA> is transported to the posterior <oocyte> and locally translated. <Oskar> organises <germ plasm> containing <RNA> and <proteins>, including <Vasa>, <Tudor> and <Nanos>. Posterior <cell nuclei> encounter this specialised <cytoplasm> and cellularise as <pole cells>. Necessity and positional sufficiency are distinguishable: loss of <Oskar> disrupts assembly, while experimentally mislocalised <oskar messenger RNA> can induce anterior <pole cells>. The latter result shows that the organising material can redirect where the programme begins; it does not mean that <Oskar> acts without the other cellular components.<Induction of germ cell formation by oskar by Anne Ephrussi and Ruth Lehmann>[Nature 358, pp. 387–392; anterior oskar localisation and ectopic germ-cell formation]{ref}
Assembly and inheritance also should not be equated with one universal granule mechanism. A <germ plasm> is a spatially organised collection of functional components; the visible granule and the whole regulatory activity are not necessarily identical. Test assembly by tracking recruitment order, deleting candidate organisers and rescuing them at physiological levels. Test specification separately by permanent <lineage tracing> and later contribution to the gonad and, where experimentally feasible, functional <gametes>. Disrupting a visible aggregate without abolishing the relevant biochemical activity is not evidence that all germline specification has failed.
In fly <pole cells>, a direct route to <transcriptional quiescence> is the small <Pgc protein>, translated from inherited germ-plasm <RNA>. It binds <P-TEFb>, a <protein kinase> complex needed for productive <RNA polymerase II> elongation, and prevents its normal recruitment to transcriptional sites. Reduced <phosphorylation> of the polymerase's C-terminal domain at serine 2 accompanies repression. Loss, ectopic expression, physical interaction and recruitment assays connect <Pgc protein> to this mechanism rather than merely correlating a silent <biological cell> with a granule.<Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells by Kazuko Hanyu-Nakamura and others>[Abstract and Results: Pgc loss and ectopic expression, P-TEFb interaction and chromatin recruitment]{ref}
The nematode <Caenorhabditis elegans> illustrates another inherited route. Maternal <PIE-1> segregates into the germline blastomeres and inhibits the somatic <transcription> programme. A repression domain with similarity to the <RNA polymerase II> C-terminal repeat provided a mechanistic link to the transcriptional apparatus; mutations that damage repression also weaken in-embryo rescue. Thus distinct inherited repressors can converge on productive <RNA polymerase II> activity. It is unnecessary to claim that <PIE-1> and <Pgc protein> are the same molecule or that every inherited germline component acts by this mechanism.<Transcriptional repression by the Caenorhabditis elegans germ-line protein PIE-1 by Ceri Batchelder and others>[Genes & Development 13, pp. 202–212; repression-domain assays and rescue with altered PIE-1]{ref}
In the <house mouse>, <primordial germ cells> are induced from competent postimplantation <epiblast> rather than assigned by an already localised maternal <germ plasm>. <BMP4> from extraembryonic <biological tissues> supplies an essential inductive input. <BMP4> null <embryos> lack <primordial germ cells>, and chimera analysis identified an extraembryonic source requirement; fewer founders in heterozygotes showed a dosage-sensitive effect on establishment rather than simply later expansion.<Bmp4 is required for the generation of primordial germ cells in the mouse embryo by Kirstie A. Lawson and others>[Abstract and chimera analysis; Genes & Development 13, pp. 424–436]{ref} Necessity of this signal does not imply that every exposed <epiblast> <biological cell> becomes germline: competence, position and competing inputs constrain the response.
The induced programme uses <BLIMP1>, <PRDM14> and <TFAP2C> to repress somatic regulatory networks and establish germline identity and <epigenetic reprogramming>. <BLIMP1> binds and represses somatic and proliferation-associated targets, while the factors also activate germline-associated programmes. This is the crucial contrast in interpreting quiescence: \b[an induced germline must transcribe its specification programme, so selective repression of somatic <genes> is not equivalent to a universal shutdown of transcription.] Chromatin and <DNA methylation> are subsequently remodelled; a hypomethylated state by itself is not evidence that the genome is transcriptionally inactive.<A tripartite transcription factor network regulates primordial germ cell specification in mice by Erna Magnúsdóttir and others>[Abstract and Results: direct BLIMP1 targets, cooperative transcription-factor activity and induction of PGC-like cells]{ref}
Induction also differs among mammals. Human <primordial germ cell-like cells> require <SOX17> as an important upstream specifier, with <BLIMP1> helping suppress alternative somatic programmes. This comes from experimentally induced <biological cells> compared with available germ-cell references; it should not be presented as direct observation of every event in an intact human <embryo>. It demonstrates why the exact mouse hierarchy cannot simply be renamed human.<SOX17 is a critical specifier of human primordial germ cell fate by Naoko Irie and others>[Cell 160, pp. 253–268; SOX17 perturbation and human primordial germ cell-like cell induction]{ref}
For either mode, measure nascent <RNA> incorporation together with serine-2-phosphorylated <RNA polymerase II>, total polymerase and multiple somatic and germline transcripts. Maternal <messenger RNA> persistence makes total <RNA> abundance an unreliable measure of current synthesis. Include somatic <biological cells> in the same <embryo> as positive controls, a validated transcription-inhibited sample as a low-signal control, and viability measurements. Timed perturbation after specification distinguishes a requirement for establishing identity from one for maintaining quiescence. Rescue should recover appropriate molecular identity and later lineage function, not merely lower a staining signal. These experiments would reveal the shared aim of suppressing inappropriate differentiation while preserving the different transcriptional requirements of inheritance and induction.
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