Local and systemic signaling in maintenance of hematopoietic progenitors

Abstract

Past work from our laboratory and that of others has established that the developing Drosophila hematopoietic organ, the lymph gland (LG), is an excellent model system for studying hematopoiesis and hematopoietic disorders. We have described the cellular components of distinct zones within the primary lobe of the developing LG: The Cortical Zone (CZ) consisting of differentiating blood cells (hemocytes); the Medullary Zone (MZ) consisting of blood progenitors that give rise to all mature blood cell types and the Posterior Signaling Center (PSC) consisting of cells of the hematopoietic niche. We have also described many different signaling pathways that control the maintenance of the blood progenitors. A highlight of this investigation was the demonstration that this maintenance requires not only a signal from the niche, but also a backward signal from the differentiating cells that we term the “equilibrium signal”.Lately, we have concentrated on systemic signals that affect hematopoiesis. A study of the effects of starvation by others and us led to an important role of insulin signaling on maintenance of blood progenitors. The principal finding was that hematopoietic progenitors sense nutritional status, both through direct sensing of amino acids by the TOR pathway, as well as indirectly by signaling through the insulin receptor.In similar studies, we have found effects of ROS signaling, hypoxia signaling and GABA signaling in the maintenance of blood progenitors. The role of GABA is interesting as it provided a direct link between the function of the olfactory system and blood progenitor maintenance. At this meeting, we will mostly discuss our unpublished data on the effect of injury on the fate of blood cells in Drosophila. Past work from our laboratory and that of others has established that the developing Drosophila hematopoietic organ, the lymph gland (LG), is an excellent model system for studying hematopoiesis and hematopoietic disorders. We have described the cellular components of distinct zones within the primary lobe of the developing LG: The Cortical Zone (CZ) consisting of differentiating blood cells (hemocytes); the Medullary Zone (MZ) consisting of blood progenitors that give rise to all mature blood cell types and the Posterior Signaling Center (PSC) consisting of cells of the hematopoietic niche. We have also described many different signaling pathways that control the maintenance of the blood progenitors. A highlight of this investigation was the demonstration that this maintenance requires not only a signal from the niche, but also a backward signal from the differentiating cells that we term the “equilibrium signal”. Lately, we have concentrated on systemic signals that affect hematopoiesis. A study of the effects of starvation by others and us led to an important role of insulin signaling on maintenance of blood progenitors. The principal finding was that hematopoietic progenitors sense nutritional status, both through direct sensing of amino acids by the TOR pathway, as well as indirectly by signaling through the insulin receptor. In similar studies, we have found effects of ROS signaling, hypoxia signaling and GABA signaling in the maintenance of blood progenitors. The role of GABA is interesting as it provided a direct link between the function of the olfactory system and blood progenitor maintenance. At this meeting, we will mostly discuss our unpublished data on the effect of injury on the fate of blood cells in Drosophila.