The cells that give rise to the gametes are often set aside during cleavage. During development, these cells will differientate into primordial germ cells, migrate to the location of the gonad, and form the germ line of the animal.
Creation of germ plasm & primordial germ cells
Cleavage in most animals segregates cells containing Germ plasm from other cells. The germ plasm effectively turns off gene expression to render the genome of the cell inert. Cells expressing Germ plasm
become primordial germ cells
(PGCs) which will then give rise to the gametes
. The germ line development in mammals, on the other hand, occurs by induction and not by an endogenous germ plasm.
Germ plasm in fruit fly
Germ plasm has been studied in detail in Drosophila. The posterior pole of the embryo contains necessary materials for the fertility of the fly. This cytoplasm, pole plasm, contains specialized materials called polar granules and the pole cells are the precursors to primordial germ cells.
Pole plasm is organized by and contains the proteins and mRNA of the posterior group genes (such as oskar, nanos gene, tudor, vasa, and valois). These genes play a role in germ line development to localize nanos mRNA to the posterior and localize germ cell determinants. Drosophila progeny with mutations in these genes fail to produce pole cells and are thus sterile, giving these mutations the name 'grandchildless'. The genes Oskar, nanos and germ cell-less (gcl) have important roles. Oskar is sufficient to recruit the other genes to form functional germ plasm. Nanos is required to prevent mitosis and somatic differentiation and for the pole cells to migrate to function as PGCs (see next section). Gcl is necessary (but not sufficient) for pole cell formation. In addition to these genes, a non-coding mRNA, polar granule component (Pgc) blocks phosphorylation and consequently activation of RNA polymerase II and shuts down transcription.
Germ plasm in amphibians
Similar germ plasm has been identified in Amphibians in the polar cytoplasm at the vegetal pole. This cytoplasm moves to the bottom of the blastocoel and eventually ends up as its own subset of endodermal cells. These cells eventually become PGCs. The presence of homologs of nanos and vasa also implicate this germ plasm as germ-determining.
Migration of primordial germ cells
The first phase of migration in Drosophila occurs when the pole cells move passively and infold into the midgut invagination. Active migration occurs through repellents and attractants. The expression of wunen
in the endoderm repels the PGCs out. The expression of columbus and hedgehog attracts the PGCs to the mesodermal precursors of the gonad. Nanos is required during migration. Regardless of PCG injection site, PGCs are able to correctly migrate to their target sites.
In zebrafish, the PGCs express two CXCR4 transmembrane receptor proteins. The signaling system involving this protein and its ligand, Sdf1, is necessary and sufficient to direct PGC migration in fish.
In frogs, the PGCs migrate along the mesentry to the gonadal mesoderm facilitated by orientated extracellular matrix with fibronectin. There is also evidence for the CXCR4/Sdf1 system in frogs.
In birds, the PGCs arise from the epiblast and migrate to anteriorly of the primitive streak to the germinal ridge. From there, they use blood vessels to find their way to the gonad. It is possible that the CXCR4/Sdf1 system is used.
Germ line development in mammals
There is no evidence of a germ plasm in mammals. This is evidence for specification of germ cells by induction. BMP
(Bone Morphogenetic Protein) signals from the extraembryonic ectoderm activate expression of fragilis
and bias the cells towards PGC. The cells expressing fragilis accumulate at the posterior of the primitive streak
and collectively express stella
via additional signals or interactions amongst themselves. Blimp1
, a general repressor of transcription is also expressed. These cells become the PGCs. The migration of these PGCs is similar to amphibians along the dorsal mesentery
to the genital ridges
. The CXCR4
system and orientation fibronectin fibers again play an important role as well as filopodia
extension. Analysis of PGC migration in different organisms concludes that the cells are guided to their target sites by cues from somatic cells along the migratory pathway.
Differentiation of primordial germ cells
In the gonads, the germ cells undergo either spermatogenesis or oogenesis depending on whether the sex is male or female respectively.
Mitotic germ stem cells, spermatogonia
, divide by mitosis to produce spermatocytes
committed to meiosis. The spermatocytes divide by meiosis to form spermatids
. The post-meiotic spermatids differientate through spermiogenesis
to become mature and functional spermatozoa
Mitotic germ stem cells, oogonia
, divide by mitosis to produce primary oocytes
committed to meiosis. Unlike sperm production, oocyte production is not continuous. These primary oocytes begin meiosis but pause in diplotene
of meiosis I
while in the embryo. All of the oogonia and many primary oocytes die before birth. After puberty in primates, small groups of oocytes and follicles prepare for ovulation by advancing to metaphase II. Only after fertilization is meiosis completed. Meiosis is asymmetric producing polar bodies and oocytes with large amounts of material for embryonic development.