Of blood cells and the nervous system

Abstract

Hematopoiesis is well-conserved between Drosophila and vertebrates. Similar as in vertebrates, the sites of hematopoiesis shift during Drosophila development. Blood cells (hemocytes) originate de novo during hematopoietic waves in the embryo and in the Drosophila lymph gland. In contrast, the hematopoietic wave in the larva is based on the colonization of resident hematopoietic sites by differentiated hemocytes that arise in the embryo, much like in vertebrates the colonization of peripheral tissues by primitive macrophages of the yolk sac, or the seeding of fetal liver, spleen and bone marrow by hematopoietic stem and progenitor cells. At the transition to the larval stage, Drosophila embryonic hemocytes retreat to hematopoietic “niches,” i.e., segmentally repeated hematopoietic pockets of the larval body wall that are jointly shared with sensory neurons and other cells of the peripheral nervous system (PNS). Hemocytes rely on the PNS for their localization and survival, and are induced to proliferate in these microenvironments, expanding to form the larval hematopoietic system. In this process, differentiated hemocytes from the embryo resume proliferation and self-renew, omitting the need for an undifferentiated prohemocyte progenitor. Larval hematopoiesis is the first Drosophila model for blood cell colonization and niche support by the PNS. It suggests an interface where innocuous or noxious sensory inputs regulate blood cell homeostasis or immune responses. The system adds to the growing concept of nervous system dependence of hematopoietic microenvironments and organ stem cell niches, which is being uncovered across phyla.

Origin and Functions of Tissue Macrophages

“…At this stage in development, macrophages are the only “white blood cell” produced, because restricted progenitors in the yolk sac give rise only to macrophages and red blood cells. This limited hematopoietic cell diversity is reminiscent of the Drosophila immune system (Makhijani and Bruückner, 2012) and indicative of the conserved origin of the yolk-sac-derived macrophage lineage. Subsequently (E8.5–E10.5), definitive hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros and give rise to all immune lineages.…”

Drosophila as a model for the two myeloid blood cell systems in vertebrates

“…Three hematopoietic waves have been described during Drosophila development, namely embryonic, larval and lymph gland hematopoiesis 2,3,23,24,30-34 . The embryonic and larval phases of hematopoiesis correspond to the formation and expansion of self-renewing ‘primitive’, or tissue-resident, macrophages (Figure 1A).…”

“…they colonize local microenvironments in peripheral tissues; and (3.) they are functional macrophages that self-renew in the differentiated state, bypassing the need for an undifferentiated progenitor 33,34 . Tissue macrophages execute all routine immune and phagocytic functions in the Drosophila larva 27,33,37 .…”

“…The self-renewal potential of tissue macrophages and other differentiated cells of ‘self-duplicating’ or ‘static’ tissues has raised considerable interest in the field of regenerative medicine 17,98,99 , but studying the underlying mechanisms has remained challenging in vertebrate systems. Lineage tracing has demonstrated that Drosophila Pxn+ embryonic macrophages persist into the larva, where they colonize local microenvironments and expand through self-renewal in the differentiated state (Figure 1A) 33,34 . Interestingly, these macrophages undergo a switch from quiescence in the embryo 23,24,33 to high proliferation in the larva, expanding from ~ 300 cells in the 1 st instar to more than 6000 cells in the 3 rd instar 23,33,34 (Brückner lab in preparation).…”

“…Lineage tracing has demonstrated that Drosophila Pxn+ embryonic macrophages persist into the larva, where they colonize local microenvironments and expand through self-renewal in the differentiated state (Figure 1A) 33,34 . Interestingly, these macrophages undergo a switch from quiescence in the embryo 23,24,33 to high proliferation in the larva, expanding from ~ 300 cells in the 1 st instar to more than 6000 cells in the 3 rd instar 23,33,34 (Brückner lab in preparation). Lineage tracing experiments did not provide any indication that Pxn+ tissue macrophages of the larva derive from undifferentiated progenitors.…”