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.
[24] The AGM region plays an important role in embryonic development, being the first autonomous intra-embryonic site for definitive haematopoiesis.
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.
[27] 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.
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.
[2][3] 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.
Furthermore, isolated organ cultures of the AGM from mouse embryos can autonomously initiate hematopoietic stem cell activity, without influence from the yolk sac or liver.
Time lapse imaging of live zebrafish embryos has provided the visualisation of haematogenic endothelium differentiating into hematopoietic stem cells.
Once these contacts dissolve, the cell, due to its apical-base polarity, moves into the subaortic space and consequently colonises other hematopoietic organs.
RUNX1 knockout studies have shown a complete removal of definitive haematopoietic activity in all foetal tissues before embryo lethality at E12.
Using conditional knockouts it was shown that the removal of Runx1 expression in AGM haemogenic endothelial cells, prevented the production of HSCs.
Nitric oxide signalling has also been shown to play a role in haemogenic endothelial cell production and activation, possibly by regulating the expression of Runx1.
This is seen in Ncx1 knockouts, where the failure to develop a heartbeat, and consequent lack of circulation results in a down-regulation of Runx1 and no haematopoietic activity in the AGM.