Tau and Futsch play non-neuronal roles in mediating morphogenesis and function of Drosophila Malpighian tubules

Tubulogenesis depends on coordinated regulation of cytoskeletal dynamics, cell polarity proteins, adhesion molecules, and extracellular matrix components. While the microtubule-associated protein Tau is well characterized in neurons, its role in non-neuronal tissues remains poorly understood. Here, we uncover a critical function of dTau in regulating the morphology and physiology of <i>Drosophila</i> Malpighian tubules, the renal analogs of vertebrates. dTau depletion by null mutation or RNAi, causes cyst-like expansions, uneven tubule diameters, and epithelial disorganization, phenotypes reminiscent of polycystic kidney disease. These changes are accompanied by cytoskeletal disarray, disrupted cell alignment, and compromised function. We also reveal partial functional redundancy between dTau and Futsch, another microtubule-associated protein, in maintaining tubules architecture. Notably, downregulation of Rho1 partially rescues dTau-associated defects, implicating coordinated function of dTau and Rho1-mediated cytoskeletal function. Our findings expand the known functions of dTau beyond nervous system and provide insights into its role in epithelial organization and tubular morphogenesis.