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

ABSTRACT: 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE280511 | GEO | 2025/08/29

REPOSITORIES: GEO

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Project description:Stem cells reside in a specialized microenvironment, called niche, which provides essential signals controlling stem cell behavior. Proper niche architecture is a key for normal stem cell function, yet only few upstream regulators are known. Here we report that the Hox transcription factor Abd-B, active in pre-meiotic spermatocytes, affects niche positioning in the Drosophila testis by regulating integrin localization in differentiated somatic cyst cells. Loss of Abd-B results in cell non-autonomous effects within the niche including centrosome misorientation in germline stem cells (GSCs) and reduced GSC divisions in larval testis, leading to a dramatic reduction of pre-meiotic stages in adult testes. By identifying Abd-B binding regions throughout the genome, we find that Abd-B mediates its effects on niche function by directly controlling at multiple levels the localization and thus signaling activity of the Sevenless (Sev) ligand, Bride of Sevenless (Boss), via its direct targets src42A and sec63. In sum, our data show for the first time that Abd-B through local signaling provides positional cues for integrin localization, which is critical for niche localization and architecture, and ensures proper niche function and GSC activity. DamID (DNA adenine methyltransferase identification) method was used to identify direct Abd-B target genes in the Drosophila 3rd instar larval testis Dam was fused to the N terminus of Abd-B and transgenic flies were generated. For identifying Abd-B targets in the Drosophila testis the fusion protein was expressed from the uninduced minimal Hsp70 promoter of the UAS vector pUAST (Brand and Perrimon, 1993). As a control for nonspecific Dam activity, transgenic flies expressing the Dam alone were used (Choksi et al., 2006). Subsequently, genomic DNA was extracted from 3rd instar larval testes, expressing either the Dam-Abd-B fusion protein or the Dam protein alone using a specific protocol (Tolhuis et al., 2011); and van Steensel personal communication). Two individual replicates, for Dam-AbdB and Dam alone, have been generated. Following a methylation-sensitive DNA digestion and PCR amplification, DNA fragments from Dam-Abd-B and control DNA were labeled and hybridized to genomic Affymetrix arrays in duplicates (Protocol available at M-bM-^@M-^\www.flychip.org.ukM-bM-^@M-^]).

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

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