Adipocyte heterogeneity regulated by the Bithorax Complex-Wnt signaling crosstalk in Drosophila

Adipocytes distributed throughout the body are essential for lipid metabolism and energy homeostasis, with regional differences affecting their functions and disease susceptibility. However, the mechanisms driving this regional heterogeneity remain poorly understood. Here, we show that the interactions between Wnt/Wingless signaling and Bithorax Complex (BX-C) genes – specifically abdominal A (abd-A) and Abdominal B (Abd-B) – drive regional differences in Drosophila larval adipocytes. Abdominal adipocytes, expressing abd-A and Abd-B, differ from thoracic ones, with active Wnt signaling further amplifying these differences. Depleting abd-A and Abd-B, genes in adipocytes reduces fat accumulation, delays larval-pupal transition, and leads to pupal lethality, while also attenuating Wnt signaling-induced lipid mobilization. Moreover, Wnt signaling stimulates abd-A and Abd-B, transcription, creating a feedforward loop that intensifies the interaction between Wnt signaling and BX-C genes. These findings elucidate how the crosstalk between cell-autonomous BX-C gene expression and Wnt signaling defines adipocyte heterogeneity in Drosophila larvae. Overall design: RNA-seq on fat bodies of control or axn/abd-A/Abd-B depleted animals. Following principal component analysis (PCA), we excluded two outlier samples from subsequent analyses: dcg+4 from the dcg+ group and dcg-AiBi-1 from the dcg-AiBi group.