Sakshi Jain, Kashish Salian, Vrushti Shah, Upendra Nongthomba
LIM domain-only (LMO) proteins are associated with chromosomal translocations in T-cell acute lymphoblastic leukaemia and are highly expressed in acute myeloid leukaemia, correlating with poor prognosis. However, their role in myeloid cell lineage specification and function remains poorly understood. Using Drosophila melanogaster, which has a single LMO protein homologue, Beadex (Bx or dLMO), and a conserved myeloid-like immune system, we investigated the in vivo role of Beadex in plasmatocytes, the macrophage-like blood cells of Drosophila. Loss of Beadex reduced lymph gland size and the area of mature plasmatocytes. RNA sequencing of Beadex knockdown haemocytes revealed transcriptional changes affecting actin cytoskeleton regulation, phagosome formation and immune response pathways. Accordingly, Beadex mutant and knockdown haemocytes exhibited reduced phagocytic index and lamellipodium area. Beadex regulates actin remodelling through transcriptional control of profilin (chickadee or chic), and profilin overexpression restored the phagocytic index to control levels. Haemocyte-specific Beadex overexpression increased susceptibility to Salmonella infection, which was associated with elevated eiger (TNF) signalling and immunopathology independent of bacterial burden. Overall, Beadex coordinates myeloid cell development, cytoskeletal dynamics and immune defence, with conserved parallels in vertebrate LMO2 biology.