Metabolic control by the Bithorax Complex-Wnt signaling crosstalk inDrosophila

Abstract

AbstractAdipocytes distributed throughout the body play crucial roles in lipid metabolism and energy homeostasis. Regional differences among adipocytes influence normal function and disease susceptibility, but the mechanisms driving this regional heterogeneity remain poorly understood. Here, we report a genetic crosstalk between theBithorax Complex(BX-C) genes and Wnt/Wingless signaling that orchestrates regional differences among adipocytes inDrosophilalarvae. Abdominal adipocytes, characterized by the exclusive expression ofabdominal A(abd-A) andAbdominal B(Abd-B), exhibit distinct features compared to thoracic adipocytes, with Wnt signaling further amplifying these disparities. Depletion ofBX-Cgenes in adipocytes reduces fat accumulation, delays larval-pupal transition, and eventually leads to pupal lethality. Depleting Abd-A or Abd-B reduces Wnt target gene expression, thereby attenuating Wnt signaling-induced lipid mobilization. Conversely, Wnt signaling stimulatedabd-Atranscription, suggesting a feedforward loop that amplifies the interplay between Wnt signaling andBX-Cin adipocytes. These findings elucidate how the crosstalk between cell-autonomousBX-Cgene expression and Wnt signaling define unique metabolic behaviors in adipocytes in different anatomical regions of fat body, delineating larval adipose tissue domains.