It takes nerve to make blood - a new Drosophila model of hematopoiesis
Does the nervous system talk to the blood? In the past, the hematopoietic and nervous systems were thought to be largely independent from each other. A recent study by HFSP postdoctoral fellow Kalpana Makhijani and colleagues from the Brückner lab now reveals that the Peripheral Nervous System (PNS) provides a crucial microenvironment for blood cell colonization and survival in the larva of the fruitfly Drosophila melanogaster. Drosophila larval hematopoiesis adds to the growing concept of nervous system dependence of hematopoietic and other organ niches, which is being uncovered across phyla.
HFSP Long-Term Fellow Kalpana Makhijani and colleagues
Hematopoiesis is well conserved between Drosophila and vertebrates. Similar to vertebrates, the sites of hematopoiesis in Drosophila shift during development. While the first and third waves of hematopoiesis in the embryo and in the Drosophila lymph gland have been well described, the origin and nature of the second wave of hematopoiesis, i.e. larval hematopoiesis, was not completely understood.
Figure: In the Drosophila larva, blood cells, or hemocytes, (red) closely colocalize with larval PNS neurons (green). The figure shows dorsal clusters of peripheral neurons of two neighboring segments, anterior is left.
When setting out to study Drosophila larval hematopoiesis, HFSP Long-Term Fellowship holder Kalpana Makhijani and colleagues made surprising findings regarding the colonization of hematopoietic sites and the dependence of blood cells on the nervous system. Using genetic lineage tracing and color-switch fluorescent live imaging, they showed that larval hematopoiesis is based on segmentally repeated epidermal-muscular pockets, hematopoietic ‘niches’ that are colonized by blood cells (hemocytes) from the embryo. Hemocytes proliferate in these locations and show a dynamic exchange, resembling the expansion and dynamics of hematopoietic stem and progenitor cells in the vertebrate bone marrow. The pattern of hemocyte localization and their preferential proliferation at these sites implied the presence of attractive, trophic and inductive signals produced by tissues of the surrounding microenvironment. Makhijani and colleagues found that cells of the peripheral nervous system jointly share epidermal-muscular pockets, and show close colocalization with hemocytes. Using genetic manipulations that disrupt peripheral neurons or that lead to ectopic neurons, they demonstrated functional dependence of larval hemocytes on the PNS with respect to hemocyte homing and trophic survival.
Nervous system mediated regulation of hematopoiesis and immune responses has been recognized in both vertebrates and lower organisms such as C. elegans, however the mechanisms of communication remain only partially understood. Work by Makhijani and colleagues from the Brückner lab has opened the doors to a new genetic model to identify the molecular signals produced by the nervous system that regulate blood development. Knowledge of the signaling mechanisms obtained from Drosophila will further our understanding of the role of the PNS in vertebrate hematopoiesis and other organ systems.
Reference
The peripheral nervous system supports blood cell homing and survival in the Drosophila larva. Makhijani, K.,Alexander, B.,Tanaka, T.,Rulifson, E. and Brückner, K. Development,138, 5379-5391.
