Primordial germ cell migration
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Primordial germ cell (PGC) migration is the process of distribution of primordial germ cells throughout the embryo during embryogenesis.
Function
Primordial germ cells are among the first lineages that are established in development[1] and they are the precursors for gametes.[2] It is thought that the process of primordial germ cell migration itself has been conserved rather than the specific mechanisms within it, as chemoattraction and repulsion seem to have been borrowed from blood cells, neurones, and the mesoderm.[1] For most organisms, PGC migration starts in the posterior (back end) of the embryo.
This process is in most cases distinct from PGC proliferation, with the exception of mammals in which both processes occur at the same time. In most mammals, specification occurs first, followed by migration, and then the proliferation process begins in the gonads.[1] PGCs interact with a wide range of cell types as they move from the epiblast to the gonads.[1] The PGCs move passively (without the need for energy) with underlying somatic cells, cross epithelial barriers, and respond to cues from their environment during active migration.[3] An epithelium must be crossed in many species during germ cell migration, and changes in adhesion are observed in PGCs during their exit from the endoderm and during the initiation of active migration.[3] Active migration takes place as PGCs move towards the developing somatic gonad.[3] Effective migration requires cell elongation and polarity.[1] Environmental guidance cues are required for the PGCs to initiate and sustain their mobility.[3] Specific molecular pathways are activated to give PGCs motility.[2]
One of the functions of PGC migration is to allow them to reach the gonad, where they will go on to form sperm or oocytes.[1] However, an additional function that this migration is thought to serve is as quality control for PGCs.[1] Migration occurs early in gametogenesis, but PGCs could contain defects that could have a negative impact on later development - genetic mutations may be acquired because of proliferation in the blastocyst.[1] This is done via a negative selection process – PGCs that are unable to complete migration are removed and those that are able to correctly respond to migration cues are preferred.[1] PGCs that are able to migrate the fastest and reach the gonad are more likely to colonise it and give rise to future gametes.[2] The PGCs that go off route or don't reach the gonad undergo programmed cell death (apoptosis). It is thought that every step after specification may function as a selective mechanism to ensure germ cells are of the highest quality.[1] The selective mechanisms may also be important for removing PGCs with abnormal epigenetic marks and in doing so preserving the germline.[1]
Primordial germ cell migration in invertebrates
In Drosophila, the whole migration process has been estimated to take 10 hours.[4] It begins with the formation of PGCs; from dividing nuclei becoming encircled by cell membranes, occurring at the posterior pole of the embryo.[5] Division of the nuclei stops once they have a cell membrane.[3] PGCs' transcription process is also thought to be actively subdued once formed.[3]
In Drosophila, PGC migration begins with passive movement along the dorsal side of the embryo, during gastrulation.[4] This is followed by more passive movement, due to the invagination of the posterior midgut primordium, which leads to the PGCs in the centre of the embryo, surrounded by epithelial cells that have been folded back on themselves.[4] There is then a split into two groups, left and right respectively, as they actively migrate laterally across the epithelium to exit the gut, facilitated by fibroblast growth factor (FGF) signalling and a repulsion-based mechanism using enzymes encoded by the Wunen gene.[3][4][6] This is followed by active movement dorsally along the basal side of the embryo.[4] Through directional migration - which requires multiple genes to work, one being the Columbus (clb) gene, which codes for Drosophila HMG CoA reductase - the germ cells move towards the somatic gonadal precursor cells and associate with them.[3][6] These two associated cell types then migrate together anteriorly, until they coalesce into the embryonic gonad at the future site of the mature gonad.[4]