In Drosophila, definitive haematopoiesis takes place in a specialized organ termed “lymph gland”. It harbours multi‐potent stem‐like blood progenitor cells whose development controls overall growth of this haematopoietic tissue and formation of mature blood cells. With respect to its development, neurotransmitters have emerged as potent regulators of blood‐progenitor cell development and function. In this study, we extend our understanding of neurotransmitters and show that progenitors are self‐sufficient with regard to synthesizing dopamine, a well‐established neurotransmitter. These cells also have modules for dopamine sensing through the receptor and transporter. We found that modulating expression of these components in progenitor cells affected lymph gland growth, which suggested growth‐promoting function of dopamine in blood‐progenitor cells. Cell‐cycle analysis of developing lymph glands revealed an unexpected requirement for intracellular dopamine in moderating the progression of early progenitor cells from S to G2 phase of the cell cycle, while activation of dopamine receptor signalling later in development regulated their progression from G2 and entry into mitosis. The dual capacity in which dopamine operated, first intracellularly to coordinate S/G2 transition and later extracellularly in G2/M transition, was critical for the growth of the lymph gland. Overall, the data presented highlight a novel non‐canonical use of dopamine in the myeloid system that reveals an uncharacterized function of intracellular dopamine in cell‐cycle phasing with outcomes on haematopoietic growth and immunity as well.

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.