Aorta-gonad-mesonephros

The aorta-gonad-mesonephros (AGM) is a region of embryonic mesoderm that develops during embryonic development from the para-aortic splanchnopleura in chick, mouse and human embryos. It has been suggested that this area, in particular the ventral wall of the dorsal aorta, is one of the primary origins of the definitive haematopoietic stem cell. The aorta-gonad-mesonephros (AGM) is a region of embryonic mesoderm that develops during embryonic development from the para-aortic splanchnopleura in chick, mouse and human embryos. It has been suggested that this area, in particular the ventral wall of the dorsal aorta, is one of the primary origins of the definitive haematopoietic stem cell. The aorta-gonad-mesonephros (AGM) region is an area derived from splanchnopleura mesoderm identified in embryonic humans, mice, and non-mammalian vertebrates such as birds and zebrafish. It contains the dorsal aorta, genital ridges and mesonephros and lies between the notochord and the somatic mesoderm, extending from the umbilicus to the anterior limb bud of the embryo. The AGM region plays an important role in embryonic development, being the first autonomous intra-embryonic site for definitive haematopoiesis. Definitive haematopoiesis produces hematopoietic stem cells that have the capacity to differentiate any blood cell lineage in the adult circulation. Specialised endothelial cells on the dorsal aorta of the AGM region, identified as haemogenic endothelium differentiate into haematopoietic stem cells. The AGM region is derived from the mesoderm layer of the embryo. During organogenesis (around the fourth week in human embryos), the visceral region of the mesoderm, the splanchnopleura, transforms into distinct structures consisting of the dorsal aorta, genital ridges and mesonephros. For a period during embryonic development, the dorsal aorta produces hematopoietic stem cells, which will eventually colonise the liver and give rise to all mature blood lineages in the adult. By birth, the dorsal aorta becomes the descending aorta, while the genital ridges form the gonads. The mesonephros go on to form nephrons and other associated structures of the kidneys. The formation of the AGM region has been best described in non-mammalian vertebrates such as Xenopus laevis. Shortly after gastrulation, cells from the dorsolateral plate, analogous to the splanchnopleura mesoderm in mammals, migrate to the midline, beneath the notochord to form the dorsal aorta, and laterally the cardinal veins and nephric ducts. The most significant function of the aorta gonad mesonephros region is its role in definitive haematopoiesis. Definitive haematopoiesis is the second wave of embryonic haematopoiesis and give rise to all hematopoietic stem cells in the adult hematopoietic system. The aorta gonad mesonephros region has been shown to harbour multipotent hematopoietic colony-forming unit-spleen (CFU-S) progenitor cells and pluripotential long-term repopulating hematopoietic stem cells (LTR-HSCs). In contrast to the yolk sac, the extra-embryonic haematopoietic site, the number of CFU-S was much greater in the aorta gonad mesonephros region. LTR-HSC activity was also found in the aorta gonad mesonephros region at a slightly earlier time than in the yolk sac and fetal liver. Thus indicating the potency of definitive haematopoiesis from this region. Furthermore, isolated organ cultures of the AGM from mice embryos can autonomously initiate hematopoietic stem cell activity, without influence from the yolk sac or liver. At 10 days post coitus (d.p.c.) the aorta gonad mesonephros region was able to initiate and expand definitive haematopoietic stem cell activity, whereas no haematopoietic activity was seen in the yolk sac until 11 d.p.c. This is the same case in human embryos, where they are first detected at day 27 in the aorta gonad mesonephros region, expand rapidly at day 35, then disappear at day 40. This “disappearance” correlates to the migration of these hematopoietic stem cells to the foetal liver, where it becomes the subsequent site of haematopoiesis. The dorsal aorta consists of an endothelial layer and an underlying stromal layer. There is also another cell population called haematogenic endothelium, which derive from the endothelial layer to produce hematopoietic stem cells.