Biology subjects

Tapadia, M. G.

Publications and source records attributed to Tapadia, M. G..

7 recordsLinked to original sources

bioRxiv2026

Tau regulates epithelial morphogenesis through vesicle trafficking dependent Notch activation

Tau is a conserved microtubule-associated protein best known for its roles in neuronal cytoskeletal stability and axonal transport. However, its functions in non-neuronal tissues remain poorly understood. Here we demonstrate that Drosophila Tau (dTau) regulates epithelial growth and tissue architecture in the Drosophila Malpighian tubules by controlling vesicular trafficking and Notch signaling. Loss of dTau results in pronounced epithelial hyperplasia, increased tubule diameter, and ectopic branching. Despite elevated Notch transcript levels, dTau-deficient tubules exhibit significantly reduced Notch intracellular domain (NICD), indicating impaired pathway activation. Proteomic and cellular analyses reveal widespread disruption of endocytic regulators and vesicle trafficking components, including reduced levels of the endocytic adaptor Liquid facets (Epsin) and altered distribution of Rab5, Rab7, and Rab11 endosomes. dTau loss also disrupts autophagic-lysosomal homeostasis and reduces endosome-lysosome fusion. These trafficking defects correlate with abnormal Delta localization and diminished Notch signaling. Together, our findings uncover a previously unrecognized role for dTau in maintaining epithelial signaling homeostasis by coordinating vesicular trafficking and receptor activation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/713835v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@d8e3b6org.highwire.dtl.DTLVardef@14de1f6org.highwire.dtl.DTLVardef@2de65aorg.highwire.dtl.DTLVardef@16e2702_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2026

Brahmi Ghrita Exerts Nephroprotective Effects by Restoring Cytoskeletal Integrity and Ion Transport in Drosophila Model of Polycystic Kidney Disease

BackgroundPolycystic kidney disease (PKD) is a genetic disorder characterized by progressive cyst formation, epithelial disorganization, and impaired fluid transport, ultimately leading to renal failure. Disruption of cytoskeletal dynamics and epithelial polarity is central to PKD pathogenesis. Malpighian tubules (MTs) of Drosophila melanogaster serve as a conserved renal analog, and caspase-3/Drice-deficient flies exhibit a robust PKD-like tubular phenotype, providing a powerful in vivo model to investigate therapeutic interventions. PurposeThis study evaluates the therapeutic potential of the Brahmi Ghrita (BG) in ameliorating PKD-like defects in Drosophila Drice mutants and elucidates the underlying cellular and molecular mechanisms. MethodsDrice mutant flies were reared with dietary BG supplementation, and developmental viability (pupation and eclosion) was assessed. Tubule morphology was analyzed by measuring cyst formation and tubule dimensions. Stellate cell (SC) number, shape, and nuclear size were quantified. Cytoskeletal organization and epithelial polarity were examined using F-actin and polarity markers. Molecular analyses included assessment of Rho1 signaling, Gelsolin, and Rho kinase (Rok) localization. Tubule physiology was evaluated by uric acid crystal deposition and Na{square}/K{square}-ATPase expression. ResultsBG supplementation significantly improved pupation and eclosion rates in Drice mutants and markedly reduced cystic dilation by restoring tubule width without altering developmental length. BG selectively increased stellate cell number and normalized aberrant morphology, while principal cell number remained unchanged. Cytoskeletal disorganization and polarity defects were rescued, accompanied by normalization of elevated Rho1 levels and restoration of the actin-severing protein Gelsolin. BG enhanced Na{square}/K{square}-ATPase expression and reduced uric acid accumulation, consistent with improved epithelial transport function. Additionally, BG promoted nuclear enrichment of Rok, indicating altered Rho-associated signaling dynamics. ConclusionBrahmi Ghrita confers nephroprotective effects in a genetic PKD model by coordinately restoring cytoskeletal integrity, epithelial polarity, and ion transport machinery. Rather than broadly suppressing Rho signaling, BG appears to rebalance the Rho1-Gelsolin axis and re-establish transport competency, culminating in structural and functional rescue. These findings provide mechanistic evidence supporting BG as a multi-target modulator of epithelial homeostasis in PKD-relevant contexts. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/705756v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1b22d58org.highwire.dtl.DTLVardef@bf1a69org.highwire.dtl.DTLVardef@5f04b4org.highwire.dtl.DTLVardef@2de776_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2025

Early disruption of neurogenesis and neural architecture by amyloid β and Tau during Drosophila development

Alzheimers disease is recognized as a late-onset neurodegenerative disorder; however, accumulating evidence suggests that disease-associated proteins may exert deleterious effects much earlier during neural development. Using a Drosophila model expressing human amyloid-{beta} and Tau, we investigated the impact of these proteins on embryonic neurodevelopment and neural stem cell dynamics. Embryos expressing amyloid-{beta} and Tau exhibited pronounced defects in axonal patterning and compromised neuronal cytoskeletal integrity, indicating early disruption of neural architecture. We observed aberrant elevation and mislocalization of the cell fate determinant Prospero, leading to premature neuronal differentiation and disruption of progenitor lineage progression. Consequently, larval brains displayed a reduced number of Prospero-positive ganglion mother cells, reflecting impaired neuroblast lineage maintenance. Cell-cycle analysis using the FUCCI system revealed altered neuroblast cell-cycle dynamics, characterized by depletion of proliferative populations and enrichment of G1-phase cells, indicative of stem cell exhaustion. In addition, increased apoptotic signaling was detected in larval neural tissues expressing amyloid-{beta} and Tau. Together, our findings demonstrate that amyloid-{beta} and Tau disrupt asymmetric division, differentiation, and self-renewal of neural stem cells during development, resulting in reduced neuronal output and defective brain organization. This study highlights that amyloid-{beta} and Tau exert neurotoxic effects early in development, providing mechanistic insight into how neurodevelopmental perturbations may contribute to later neurodegeneration.

developmental biology↗

bioRxiv2025

Caspase-3/Drice as a critical regulator of actin dynamics through its dual control of small RhoGTPase family and Gelsolin in the Malpighian tubules of Drosophila.

Caspases are executioner enzymes primarily known for their role in driving programmed cell death. However, they are now also known to regulate plethora of non-apoptotic functions such as proliferation, differentiation, endocytic trafficking, cell polarity, morphogenesis, inflammatory response and immune response. Here, in this study we report the role of Drosophila caspase 3, Drice, in spatial and dynamic regulation of actin filaments during development and proper functioning of the Malpighian tubules (MTs) of Drosophila melanogaster. Previously, we showed that Drice is crucial for the morphogenesis of the MTs, and its absence results in erroneous RhoGTPase signaling driving disarray in actin organization, this led to the formation of multiple fluid filled cysts in tubules. In the present study, we show that altered expression of two member of the Rho family of small GTPases, Rho1 and CDC42, perturbs the downstream signaling cascade. Reduced expression of Rok aborts the Rho1 signaling in Drice null mutants, whereas enhanced expression of CDC42 results in Arp2/3-driven hyper-polymerization of actin filaments. We compared Rho-GTPase interacting partners in Oregon R+ (Control) and Drice mutants, and identified the absence of Gelsolin-Rho1 interaction in Drice mutants. Moreover, its expression was significantly downregulated, in the MTs. These factors collectively influence the F-actin to G-actin ratio, which significantly affects actin organization in the MTs. These results demonstrate the crucial role of caspase-3/Drice in maintaining actin homeostasis and tubule morphogenesis. This study highlights the importance of caspase activity beyond apoptosis and its potential function in the developmental and physiological processes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/679759v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@162c4b2org.highwire.dtl.DTLVardef@15fabdcorg.highwire.dtl.DTLVardef@c0ec3org.highwire.dtl.DTLVardef@19d2f83_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

Tau mediated regulation of Rho1- cytoskeletal dynamics in shaping renal tubule development in Drosophila

The present study explored the significance of the microtubule-associated protein Tau in the morphogenesis and physiological processes of Malpighian tubules (MTs) in Drosophila melanogaster. Employing genetic manipulation techniques and microscopy, we established that Tau plays a crucial role in MTs development and function. Genetic ablation and RNAi-mediated suppression of Tau led to pronounced structural abnormalities, including cystic formations, non-uniform tubule diameters, and disorganized epithelial architecture. These aberrations are accompanied by perturbations in the cytoskeletal arrangement, compromised cellular polarity, and ionic imbalances. Functional analyses revealed deficiencies in salt homeostasis and fluid secretion within Tau-deficient tubules. Attenuation of Rho1 expression mitigated the structural defects observed in Tau mutants, highlighting the importance of Tau in modulating Rho1-mediated actin-microtubule dynamics suggesting a genetic interplay between Tau and Rho1 GTPase in orchestrating tubule morphogenesis The phenotypic parallels between Tau-deficient MTs and mammalian models of polycystic kidney disease implies an evolutionarily conserved function of Tau in tubular organ biology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/634261v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1f4afc6org.highwire.dtl.DTLVardef@1402eb7org.highwire.dtl.DTLVardef@bb089dorg.highwire.dtl.DTLVardef@1328b2e_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2020

Non-apoptotic function of caspase-3 in morphogenesis of epithelial tubes of Drosophila renal system

Cells trigger apoptosis to eliminate themselves from the system, when tissue needs to be sculptured or they detect any abnormality within them, thus preventing irreparable damage to the host. Drosophila Malpighian tubules express apoptotic proteins, without succumbing to cell death. Here we present evidence to show apoptosis independent role of executioner caspase, Drice, for precise architecture and function of Malpighian tubules. Drice is required for precise cytoskeleton organization and convergent extension, failing which the morphology, size, cellular number and arrangement gets affected. Acquisition of star shape of stellate cells in adult Malpighian tubules requires Drice. We demonstrate that Drice regulates expression of Rho1GTPase and localization of polarity proteins. Our study shows a probable mechanism by which Drice governs tubulogenesis via Rho1GTPase mediated coordinated organization of actin cytoskeleton and membrane stablisation. Furthermore, defective morphology of tubules leads to abnormal osmoregulation and excretory functions. Collectively our findings suggest a possible non-apoptotic function of caspase-3 in the fine tuning of cell mobility during tubule development and our results will add to the growing understanding of diverse roles of caspases during its evolution in metazoans.

developmental biology↗

bioRxiv2019

Characterisation of l(3)tb as a novel tumour suppressor allele of DCP2 in Drosophila melanogaster

Mutants provide an excellent platform for the discovery and characterization of gene functions. The present communication is a pioneering treatise on a hitherto undescribed function of the gene coding for the mRNA decapping protein 2 (DCP2) in Drosophila melanogaster. DCP2, the gene coding for the mRNA decapping enzyme, has been studied in various model organisms in the light of maintenance of transcript abundance and stability but has never been implicated in tumourigenesis. Herein, we describe the mapping and characterization of a novel tumour suppressor allele of DCP2 (CG6169), which we named as lethal(3)tumorous brain [l(3)tb]. The homozygous mutant individuals show prolonged larval life, develop larval brain tumors and are lethal in the larval/pupal stages. The tumour is characterized by the presence of increased number of superficial neuroblasts, abnormal chromosomal condensation and causes overgrowth in the wing and the eye-antennal discs of the homozygous mutant larvae, all of which are rescued by the introduction of a functional copy of DCP2 in the mutant background, thereby establishing the causal role of the mutation and providing a genetic validation of the allelism. Our findings therefore ascribe a novel role of tumor suppression to DCP2 besides its cognate function of mRNA decapping and thereby identify it as a potential candidate for future research on tumorigenesis.

genetics↗