Primordial germ cell (PGC) migration is the process of distribution of primordial germ cells throughout the embryo during embryogenesis.
Primordial germ cell (PGC) migration is the process of distribution of primordial germ cells throughout the embryo during embryogenesis.
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]
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]
In vertebrate development, the location where primordial germ cells are specified and the subsequent migratory paths that they take differs among species. [1]
Chicken primordial germ cells are initially specified in the area pellucida (a one-cell thick layer of epiblast lying above the sub-germinal space). [1] [7] Following the formation of the primitive streak, the germ cells are carried to the germinal crescent region. [1] Unlike most model organisms where germ cell migration is predominantly via the gut epithelium, chicken PGCs migrate through the embryonic vascular epithelium. [3] Once they have exited the capillary vessels, the final stage of migration is along the dorsal mesentery to the developing gonad. [1]
In mice, PGCs are specified in the proximal epiblast and subsequently migrate through the primitive streak towards the endoderm. [3] The PGCs then embed themselves within the epithelium of the hind-gut and from there will migrate towards the mesoderm via the dorsal mesentery. [1] [3] There is then bilateral migration of the PGCs to the developing gonadal ridges which follows a pattern very similar to that found in Drosophila. [1]
Zebrafish PGCs are specified at four different locations within the early embryo via inheritance of germ plasm (a mixture of RNA and protein often associated with mitochondria). [8] [3] Germ cells from these four locations will then migrate dorsally after down-regulation of the rgs14a G-protein which regulates E-cadherin. [1] Down-regulation will result in reduced cell-cell adhesion which allows the germ cells to separate and begin the migration process. Migration of the PGCs then continues towards the developing somites 1-3. [9] This movement is coordinated by the expression of the chemo-attractant SDF1A (stromal derived factor 1a). [3] The final migration towards the developing gonad occurs 13 hours-post-fertilisation after which point the germ cells coalesce with the somatic gonadal precursor cells. [3] The entire process takes around 24 hours. [3]
PGCs are described as the dedicated cells in early embryonic development, responsible for reaching the developing gonad. [3] [9] During their migration however, heterogeneity of cellular behaviour is observed due to change in cellular morphology from the time of specification to colonization. [3] By the end of PGC migration, around 5% of migratory cells remain outside the gonad and later undergo apoptosis. [10]
The apoptotic route during the migratory period is occurring via an intrinsic pathway; nonetheless, the elimination of PGCs can be unsuccessful and result in tumour formation known as teratomas, derivatives of the three germ layers. [1] [11] Mutations in Pten, CyclinD1, Dmrt1 and Dnd1 oncogenes in mice resulted in testicular teratomas, and variants are related with the same tumours in humans. [1] Tumour formation (neoplasm) from foetal gonocytes suggests that they are incapable of maintaining proliferative arrest and resistance to further differentiation. [1]
Even so, the origin of these teratomas could be distinct from the PGCs failing in migration. [12] Extragonadal germ cell tumours (GCTs) evolve due to a lesion along the midline of the body, prior to the migratory PGCs movement through the hindgut and the medial mesentery to the gonads. [3] Therefore, human GCTs originate from early embryo stem cells and the germ line, and unlike most tumours they seldom have somatic mutations, but instead are driven by unsuccessful control of their developmental potential, resulting in their reprogramming. [3]
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.
Gastrulation is the stage in the early embryonic development of most animals, during which the blastula, or in mammals the blastocyst is reorganized into a two-layered or three-layered embryo known as the gastrula. Before gastrulation, the embryo is a continuous epithelial sheet of cells; by the end of gastrulation, the embryo has begun differentiation to establish distinct cell lineages, set up the basic axes of the body, and internalized one or more cell types including the prospective gut.
A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.
In biology and genetics, the germline is the population of a multicellular organism's cells that pass on their genetic material to the progeny (offspring). In other words, they are the cells that form the egg, sperm and the fertilised egg. They are usually differentiated to perform this function and segregated in a specific place away from other bodily cells.
A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans produce two or three primary germ layers. Some animals, like cnidarians, produce two germ layers making them diploblastic. Other animals such as bilaterians produce a third layer between these two layers, making them triploblastic. Germ layers eventually give rise to all of an animal's tissues and organs through the process of organogenesis.
Gametogonium are stem cells for gametes located within the gonads. They originate from primordial germ cells, which have migrated to the gonads. Male gametogonia which are located within the testes during development and adulthood are called spermatogonium. Female gametogonia, known as oogonium, are found within the ovaries of the developing foetus and were thought to be depleted at or after birth. Spermatogonia and oogonia are classified as sexually differentiated germ cells.
An oogonium is a small diploid cell which, upon maturation, forms a primordial follicle in a female fetus or the female gametangium of certain thallophytes.
The primitive node is the organizer for gastrulation in most amniote embryos. In birds it is known as Hensen's node, and in amphibians it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in amphibians, or by the posterior marginal zone in amniotes including birds.
The border cells are a cluster of 6–8 cells that migrate in the ovariole of the fruit-fly Drosophila melanogaster, during the process of oogenesis. A fly ovary consists of a string of ovarioles or egg chambers arranged in an increasing order of maturity. Each egg chamber contains 16 central germline, nurse cells surrounded by a monolayer epithelium of nearly 1000 follicle cells. At stage 8 of oogenesis, these cells initiate invading the neighbouring nurse cells, and reach the oocyte boundary by Stage 10.
In amniote embryonic development, the epiblast is one of two distinct cell layers arising from the inner cell mass in the mammalian blastocyst, or from the blastula in reptiles and birds, the other layer is the hypoblast. It drives the embryo proper through its differentiation into the three primary germ layers, ectoderm, mesoderm and endoderm, during gastrulation. The amniotic ectoderm and extraembryonic mesoderm also originate from the epiblast.
Mesenchyme is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every organ in the developing embryo.
In developmental biology, the cells that give rise to the gametes are often set aside during embryonic cleavage. During development, these cells will differentiate into primordial germ cells, migrate to the location of the gonad, and form the germline of the animal.
The development of fishes is unique in some specific aspects compared to the development of other animals.
Human embryonic development, or human embryogenesis, is the development and formation of the human embryo. It is characterised by the processes of cell division and cellular differentiation of the embryo that occurs during the early stages of development. In biological terms, the development of the human body entails growth from a one-celled zygote to an adult human being. Fertilization occurs when the sperm cell successfully enters and fuses with an egg cell (ovum). The genetic material of the sperm and egg then combine to form the single cell zygote and the germinal stage of development commences. Embryonic development in the human, covers the first eight weeks of development; at the beginning of the ninth week the embryo is termed a fetus. The eight weeks has 23 stages.
In amniote embryology, the hypoblast is one of two distinct layers arising from the inner cell mass in the mammalian blastocyst, or from the blastodisc in reptiles and birds. The hypoblast gives rise to the yolk sac, which in turn gives rise to the chorion.
The development of the gonads is part of the prenatal development of the reproductive system and ultimately forms the testicles in males and the ovaries in females. The gonads initially develop from the mesothelial layer of the peritoneum.
Gonocytes are the precursors of spermatogonia that differentiate in the testis from primordial germ cells around week 7 of embryonic development and exist up until the postnatal period, when they become spermatogonia. Despite some uses of the term to refer to the precursors of oogonia, it was generally restricted to male germ cells. Germ cells operate as vehicles of inheritance by transferring genetic and epigenetic information from one generation to the next. Male fertility is centered around continual spermatogonia which is dependent upon a high stem cell population. Thus, the function and quality of a differentiated sperm cell is dependent upon the capacity of its originating spermatogonial stem cell (SSC).
Vasa is an RNA binding protein with an ATP-dependent RNA helicase that is a member of the DEAD box family of proteins. The vasa gene is essential for germ cell development and was first identified in Drosophila melanogaster, but has since been found to be conserved in a variety of vertebrates and invertebrates including humans. The Vasa protein is found primarily in germ cells in embryos and adults, where it is involved in germ cell determination and function, as well as in multipotent stem cells, where its exact function is unknown.
Ruth Lehmann is a developmental and cell biologist. She is the Director of the Whitehead Institute for Biomedical Research. She previously was affiliated with the New York University School of Medicine, where she was the Director of the Skirball Institute of Biomolecular Medicine, the Laura and Isaac Perlmutter Professor of Cell Biology, and the Chair of the Department of Cell Biology. Her research focuses on germ cells and embryogenesis.
The germ cell nest forms in the ovaries during their development. The nest consists of multiple interconnected oogonia formed by incomplete cell division. The interconnected oogonia are surrounded by somatic cells called granulosa cells. Later on in development, the germ cell nests break down through invasion of granulosa cells. The result is individual oogonia surrounded by a single layer of granulosa cells. There is also a comparative germ cell nest structure in the developing spermatogonia, with interconnected intracellular cytoplasmic bridges.