[1] The development of the lymphatic system has been a highly debated topic in developmental biology for a long time.
Previously, it was debated whether the lymph sacs developed from the venous system, or if they came from spaces in the mesenchyme, which come together in a centripetal direction and secondarily opened into the veins.
[4] Because lymph sacs form from the venous system, they typically contain red blood cells.
[4] Studies have shown that the development of lymph sacs occurs through swelling and outgrowth of pre-lymphatic clusters from the cardinal vein, in a process termed ballooning.
[1] Homologs of this transcription factor have been found in humans, chicks, newts, frogs, Drosophila, and zebrafish.
[1] However, regardless of the presence of these markers, it appears that only the subset of endothelial cells that begin to express Prox1 form the undeveloped lymph sacs.
[1] Many experiments involving mice have proven the importance of the Prox1 transcription factor in the development of primitive lymph sacs.
It is believed that Prox1 is the single most important transcription factor that programs the fate of endothelial cells becoming lymphatic components.