Dual control exerted by dopamine in blood-progenitor cell cycle regulation inDrosophila

Abstract

In Drosophila, definitive hematopoiesis occurs in a specialized organ termed "lymph gland", where multi-potent stem-like blood progenitor cells reside and their homeostasis is central to growth of this organ. Recent findings have implicated a reliance on neurotransmitters in progenitor development and function however, our understanding of these molecules is still limited. Here, we extend our analysis and show that blood-progenitors are self-sufficient in synthesizing dopamine, a well-established neurotransmitter and have modules for its sensing through receptor and uptake via, transporter. Modulating their expression in progenitor cells affects lymph gland growth. Progenitor cell cycle analysis revealed an unexpected requirement for intracellular dopamine in progression of early progenitors from S to G2 phase of the cell cycle, while activation of dopamine-receptor later in development regulated the progression from G2 to entry into mitosis. The dual capacity in which dopamine operates, both intra-cellularly and extra-cellularly, controls lymph gland growth. These data highlight a novel and non-canonical use of dopamine as a proliferative cue by the myeloid-progenitor system and reveals a functional requirement for intracellular dopamine in cell-cycle progression.

Gcm alleviates the inflammatory phenotype induced by Toll activation inDrosophilahemocytes

“…Our data do not allow to distinguish if the signal is transmitted through direct neuron-hemocyte connection or through systemic acetylcholine secretion. Several neurotransmitters are secreted systemically in the hemolymph (71) and can be produced by the hemocytes themselves (72, 73), but this was never shown for acetylcholine in the hemolymph and our transcriptomic data indicate that ChAT is not expressed in hemocytes. A recent study in adult Drosophila shows that other tissues than neurons produce acetylcholine and that both neuronal and glia derived acetylcholine regulates the Toll mediated immune response of hemocytes through nAch receptor (76).…”

“…This autocrine process is mediated by the receptors 5-HT1B and 5-HT2B (72). At last, Dopamine signaling is used by the progenitors in the lymph gland to regulate cell cycle (73).…”

Gcm counteracts Toll-induced inflammation and impacts hemocyte number through cholinergic signaling

“…Our data do not allow to distinguish if the signal is transmitted through direct neuron–hemocyte connection or through systemic acetylcholine secretion. Several neurotransmitters are secreted systemically in the hemolymph ( 73 ) and can be produced by the hemocytes themselves ( 74 , 75 ), but this was never shown for acetylcholine in the hemolymph, and our transcriptomic data indicate that ChAT is not expressed in hemocytes. A recent study in adult Drosophila shows that tissues other than neurons produce acetylcholine and that both neuronal and glia-derived acetylcholine regulates the Toll-mediated immune response of hemocytes through nAch receptors ( 78 ).…”

“…This autocrine process is mediated by the receptors 5-HT1B and 5-HT2B ( 74 ). At last, dopamine signaling is used by the progenitors in the lymph gland to regulate the cell cycle ( 75 ).…”