Dual control of dopamine in Drosophila myeloid-like progenitor cell proliferation and regulation of lymph gland growth

In Drosophila, definitive hematopoiesis takes place in "lymph gland". It harbours progenitor cells whose development controls its growth and formation of mature blood cells. With respect to its development, neurotransmitters have emerged as regulators of blood-progenitor development and function. In this study, we investigate neurotransmitter dopamine and show that progenitors are self-sufficient with regards to synthesising it. These cells have modules for dopamine sensing through the receptor, transporter. We found that modulating expression of these components in progenitor cells affected lymph gland growth, which suggested its growth-promoting function. Cell-cycle analysis of developing lymph glands revealed a requirement for intracellular-dopamine in moderating the progression of early progenitor cells from S-G2 phase of cell-cycle, while activation of dopamine receptor signaling later in development regulated their progression from G2-M. The dual capacity in which dopamine operated intracellularly to coordinate S-G2 transition and extracellularly in G2-M transition, was critical for the lymph gland growth. Overall, a non-canonical use of dopamine in the myeloid system shows an uncharacterized function of intracellular-dopamine in cell-cycle phasing with outcomes on hematopoietic growth, immunity.