Browsing by Author "Mousumi Mutsuddi"

Now showing 1 - 20 of 52

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function
(John Wiley and Sons Inc, 2018) Vincenzo Salpietro; Stephanie Efthymiou; Andreea Manole; Bhawana Maurya; Sarah Wiethoff; Balasubramaniem Ashokkumar; Maria Concetta Cutrupi; Valeria Dipasquale; Sara Manti; Juan A. Botia; Mina Ryten; Jana Vandrovcova; Oscar D. Bello; Conceicao Bettencourt; Kshitij Mankad; Ashim Mukherjee; Mousumi Mutsuddi; Henry Houlden
We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.
A novel mutation in FRMD7 causes X-linked idiopathic congenital nystagmus in a North Indian family
(Elsevier Ireland Ltd, 2015) Shashank Gupta; Ekta Pathak; Vidya Nair Chaudhry; Prashaant Chaudhry; Rajeev Mishra; Abhishek Chandra; Ashim Mukherjee; Mousumi Mutsuddi
Idiopathic congenital nystagmus (ICN) is the most common form of oculomotor disorder characterized by involuntary bilateral ocular oscillations. Primarily the disease is an ocular anomaly but the pathophysiology is associated with neuronal cytoskeletal dynamics in the brain. In the current study, a three generation North Indian family affected with X-linked idiopathic congenital nystagmus (XLICN) was recruited. Our aim was to identify the causal mutation for ICN in the family by screening the candidate gene, FERM domain containing-7 (. FRMD7). This gene has been implicated in XLICN as it regulates neuronal cytoskeletal proteins and neurite outgrowth in the developing brain. Therefore, the entire protein coding region, including splice junctions, 5' UTR and 3' UTR of FRMD7 was screened by PCR-Sanger sequencing. Targeted sequencing revealed a novel A to G transition in the exon seven (c.556A.>. G), resulting in a conservative substitution of methionine by valine at codon 186 (p.M186V). A cohort of healthy individuals was also checked for presence of the putative causal variant by allele specific PCR. All the affected males and carriers in the family shared this variant; however, this was absent in the unaffected males as well as 100 unrelated healthy individuals. Further, protein homology modeling revealed that the change p.M186V might destabilize the interaction between the FERM-M and FERM-C domains. The in silico prediction supports pathogenicity of the mutation; nevertheless it needs in vivo validation in the future. This is the first genetic investigation of XLICN in a North Indian family where we report a novel causal mutation c.556A. >. G (p.M186V) in the gene FRMD7. © 2015 Elsevier Ireland Ltd.
Ayurvedic amalaki rasayana and rasa-Sindoor suppress neurodegeneration in fly models of Huntington's and Alzheimer's diseases
(2013) Vibha Dwivedi; Bipin K. Tripathi; Mousumi Mutsuddi; Subhash C. Lakhotia
We examined two Ayurvedic Rasayana formulations, claimed to facilitate 'healthy ageing', for their role in neuroprotection in fly models of polyQ (127Q and Huntington's) and Alzheimer's disorders. Our earlier findings showed that dietary supplement of Amalaki Rasayana, a preparation derived from Indian gooseberry fruits, and Rasa-Sindoor, an organo-metallic Bhasma prepared from mercury and sulphur, improves general well-being of fruit flies. Here we show that dietary supplement of either of these formulations during larval period substantially suppressed neurodegeneration in fly models of polyQ and Alzheimer's disorders without any side-effects. Dietary Amalaki Rasayana or Rasa-Sindoor prevented accumulation of inclusion bodies and heat shock proteins, suppressed apoptosis, elevated the levels of heterogeneous nuclear ribonucleoproteins and cAMP response element binding protein and at the same time improved the ubiquitin-proteasomal system for better protein clearance in affected cells. Our studies suggest, the potential of these Ayurvedic formulations in providing a holistic relief from the increasingly common neurodegenerative disorders.
Chip physically interacts with Notch and their stoichiometry is critical for Notch function in wing development and cell proliferation in Drosophila
(Elsevier, 2015) Nalani Sachan; Abhinava K. Mishra; Mousumi Mutsuddi; Ashim Mukherjee
Background Notch signaling plays a fundamental role both in metazoan cell fate determination and in the establishment of distinct developmental cell lineages. In a yeast two-hybrid screen, we identified Chip as a binding partner of Notch. Thus, we investigated the functional significance of Notch and Chip interactions. Methods Co-immunoprecipitation and GST pull-down experiments confirmed the physical interaction between Notch and Chip. Immunostaining revealed that Chip and Notch-intracellular domain (Notch-ICD) co-localized in cell nuclei. Loss-of-function and gain-of-function analyses of Chip were carried out using FLP/FRT and GAL4-UAS systems, respectively. Immunostaining and real-time PCR were performed to analyze the role of Chip on Notch-induced cell proliferation. Results Here, we report transcriptional cofactor Chip as a novel binding partner of Notch. Chip and Notch also showed strong genetic interactions, and Chip mutant clones in the dorsal compartment induced ectopic wing margins by ectopic expression of Notch and its targets, Wg and Cut. Our analyses revealed that stoichiometry of Notch and Chip is critical at the dorso-ventral (DV) boundary for wing margin formation. In addition, overexpression of Chip can rescue Notch-induced cell proliferation in larval imaginal discs. Conclusions Our results indicate that Notch function in the DV boundary area is presumably dependent on Notch-Chip heterodimer formation. In addition, overexpression of Chip can rescue Notch-induced cell proliferation, presumably through titration of overexpressed Notch-ICD by excess Chip molecules. General Significance: The present study reveals that Chip is a novel interacting partner of Notch and it plays a major role in Notch-induced DV margin formation and cell proliferation. © 2015 Published by Elsevier B.V.
Deltex cooperates with TRAF6 to promote apoptosis and cell migration through Eiger-independent JNK activation in Drosophila
(Blackwell Publishing Ltd, 2021) Vartika Sharma; Mousumi Mutsuddi; Ashim Mukherjee
JNK signaling is a highly conserved signaling pathway that regulates a broad spectrum of cellular processes including cell proliferation, migration, and apoptosis. In Drosophila, JNK signaling is activated by binding of the tumor necrosis factor (TNF) Eiger to its receptor Wengen, and a conserved signaling cascade operates that culminates into activation of dual phosphatase Puckered thereby triggering apoptosis. The tumor necrosis factor receptor (TNFR) associated factor 6 (TRAF6) is an adaptor protein, which transduces the signal from TNFRs and Toll-like receptor/interleukin-1 receptor superfamily to induce a wide spectrum of cellular responses. TRAF6 also acts as the adaptor protein that mediates Eiger/JNK signaling in Drosophila. In a genetic interaction study, deltex (Dx) was identified as a novel interactor of TRAF6. Dx is well known to regulate Notch signaling in a context-dependent manner. Our data suggest that combinatorial action of Dx and TRAF6 enhances the Dx-induced wing nicking phenotype by inducing caspase-mediated cell death. Co-expression of Dx and TRAF6 also results in enhanced invasive behavior and perturbs the normal morphology of cells. The cooperative action of Dx and TRAF6 is attributed to JNK activation, which also leads to ectopic wingless (Wg) and decapentaplegic (Dpp) expression. Our results also reveal that the endocytic pathway component Rab7 may play a pivotal role in the regulation of Dx–TRAF6-mediated activation of JNK signaling. Here, we present the fact that Dx and TRAF6 together activate JNK signaling in an Eiger-independent mechanism. © 2020 International Federation for Cell Biology
Deltex interacts with Eiger and consequently influences the cell death in Drosophila melanogaster
(Elsevier Inc., 2018) Debdeep Dutta; Ankita Singh; Maimuna Sali Paul; Vartika Sharma; Mousumi Mutsuddi; Ashim Mukherjee
TNF-JNK signaling is one of the highly conserved signaling pathways that regulate a broad spectrum of cellular processes including proliferation and apoptosis. Eiger, the sole homologue of TNF in Drosophila, initiates the TNF-JNK pathway to induce cell death. Previously, Deltex (Dx) has been identified as a Notch signaling component that regulates vesicular trafficking of Notch. In the present study, we have investigated the interaction between these two proteins in order to identify how Dx influences the activity of Eiger. Dx is found to act as a novel modulator of JNK-mediated cell death inducing activity of Eiger. Additionally, we observe that dx genetically interacts with eiger during wing development, and these two proteins, Dx and Eiger, colocalize in the cytoplasm. Our analysis reveals that Dx is involved in the cytoplasmic relocalization of Eiger from the cell membrane, thereby influencing Eiger-mediated JNK-activation process. Moreover, we demonstrate that Dx potentiates the activity of Eiger to downregulate Notch signaling pathway by retaining the Notch protein in the cytoplasm. Together, our findings reveal a novel role of Dx to modulate the signaling activity of Eiger and subsequent JNK-mediated cell death. © 2018
Deltex modulates Dpp morphogen gradient formation and affects Dpp signaling in Drosophila
(Company of Biologists Ltd, 2022) Vartika Sharma; Bappi Sarkar; Mousumi Mutsuddi; Ashim Mukherjee
Deltex (Dx) is a context-dependent regulator of Notch signaling that can act in a non-canonical fashion by facilitating the endocytosis of the Notch receptor. In an RNAi-based modifier screen of kinases and phosphatases, we identified Thickveins (Tkv), the receptor of Decapentaplegic (Dpp), as one of the interactors of Dx. Dpp, a Drosophila homolog of TGF-β and bone morphogenetic proteins, acts as a morphogen to specify cell fate along the anterior-posterior axis of the wing. Tight regulation of Dpp signaling is thus indispensable for its proper functioning. Here, we present Dx as a novel modulator of Dpp signaling. We show evidence for the very first time that dx genetically interacts with dpp and its pathway components. Immunocytochemical analysis revealed that Dx colocalizes with Dpp and its receptor Tkv in Drosophila third-instar larval tissues. Furthermore, Dxwas also seen to modulate the expression of dpp and its target genes, and we attribute this modulation to the involvement of Dx in the endocytosis and trafficking of Dpp. This study thus presents awhole newavenue of Dpp signaling regulation via the cytoplasmic protein Dx. © 2022. Published by The Company of Biologists Ltd | Journal of Cell Science.
Deltex positively regulates Toll signaling in a JNK independent manner in Drosophila
(Blackwell Publishing Ltd, 2021) Vartika Sharma; Mousumi Mutsuddi; Ashim Mukherjee
Toll pathway is the center for the function of immune system in both Drosophila and mammals. Toll pathway in Drosophila gets activated upon binding of the ligand Spätzle to the receptor, Toll, triggering a series of proteolytic cascade culminating into the activation of the NF-κB factors Dorsal and/or Dif (Dorsal-related immunity factor). Inappropriate activation of the Toll pathway is often associated with systemic inflammation phenotype in the absence of infection, and thus, it is important to understand the regulation of Toll signaling. Deltex (Dx) is a context-dependent regulator of Notch signaling and has been linked with cell-mediated immunity in the mammalian system lately. However, the unambiguous role of Dx in humoral and cell-mediated immunity is yet to be explored. Our study unravels the novel role of Dx in Toll pathway activation. Gain of function of dx in Drosophila larvae results in increased melanotic mass formation and increased lamellocyte production. Our results also reveal the nuclear accumulation of transcription factors Dorsal and Dif and expression of Toll-associated antimicrobial peptides (AMP) in Dx over-expression background. Further, we also tried to elucidate the role of Dx in JNK-independent Toll activation. Here we present Dx as a novel candidate in the regulation of Toll pathway. © 2021 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd
DLin52 is crucial for dE2F and dRBF mediated transcriptional regulation of pro-apoptotic gene hid
(Elsevier, 2014) Pradeep Kumar Bhaskar; Satya Surabhi; Bipin Kumar Tripathi; Ashim Mukherjee; Mousumi Mutsuddi
Drosophila lin52 (dlin52) is a member of Myb transcription regulator complex and it shows a dynamic pattern of expression in all Drosophila tissues. Myb complex functions to activate or repress transcription in a site-specific manner; however, the detailed mechanism is yet to be clearly understood. Members of the Drosophila melanogaster Myb-MuvB/dREAM complex have been known to regulate expression of a wide range of genes including those involved in regulating apoptosis. E2F and its corepressor RBF also belong to this complex and together they regulate expression of genes involved in cell cycle progression, apoptosis, differentiation, and development. In the present study, we examined whether the depletion of dlin52 in developing photoreceptor neurons results in enhanced apoptosis and disorganisation of the ommatidia. Strikingly, we found that dLin52 is essential for transcriptional repression of the pro-apoptotic gene, hid; decrease in dlin52 levels led to dramatic induction of hid and apoptosis in eye-antennal discs. Reduction of Rpd3 (HDAC1), another member of the dREAM complex, also led to marginal upregulation of Hid. In addition, we also demonstrated that an optimum level of dLin52 is needed for dE2F1/2 activity on the hid promoter. dlin52 cooperates with dRBF and dE2F1/2 for recruitment of repressor complex on the hid promoter. Preliminary data indicate that Rpd3/HDAC1 also contributes to hid repression. Based on the findings, we conclude that dLin52 functions as a co-factor and modulates activity of members of dMyb/dREAM complex at hid promoter, thus regulating apoptosis by repressing this pro-apoptotic gene in the developing Drosophila eye. © 2014 Elsevier B.V.
Drosophila pelle phosphorylates Dichaete protein and influences its subcellular distribution in developing oocytes
(2010) Mousumi Mutsuddi; Ashim Mukherjee; Baohe Shen; James L. Manley; John R. Nambu
The Drosophila Dichaete gene encodes a member of the Sox family of high mobility group (HMG) domain proteins that have crucial gene regulatory functions in diverse developmental processes. The subcellular localization and transcriptional regulatory activities of Sox proteins can be regulated by several post-translational modifications. To identify genes that functionally interact with Dichaete, we undertook a genetic modifier screen based on a Dichaete gain-offunction phenotype in the adult eye. Mutations in several genes, including decapentaplegic, engrailed and pelle, behaved as dominant modifiers of this eye phenotype. Further analysis of pelle mutants revealed that loss of pelle function results in alterations in the distinctive cytoplasmic distribution of Dichaete protein within the developing oocyte, as well as defects in the elaboration of individual egg chambers. The death domain-containing region of the Pelle protein kinase was found to associate with both Dichaete and mouse Sox2 proteins, and Pelle can phosphorylate Dichaete protein in vitro. Overall, these findings reveal that maternal functions of pelle are essential for proper localization of Dichaete protein in the oocyte and normal egg chamber formation. Dichaete appears to be a novel phosphorylation substrate for Pelle and may function in a Pelle-dependent signaling pathway during oogenesis. © 2010 UBC Press.
Dynamic pattern of expression of dlin52, a member of the Myb/MuvB complex, during Drosophila development
(2012) Pradeep Kumar Bhaskar; Ashim Mukherjee; Mousumi Mutsuddi
The DREAM (DP, RB, E2F and MuvB) complex is required in humans to arrest the expression of cell cycle genes during quiescence. One of its members LIN52 has been isolated from the repressor complex but little is known about its molecular function. It has been reported recently that the serine residue 28 of LIN52 is phosphorylated by DYRK1A, and point mutation of this residue or down regulation of DYRK1A (which phosphorylates LIN52) leads to disruption of DREAM complex assembly, which is needed for G 0 arrest. Function of all the members of the dMyb complex (homologue of DREAM complex) in Drosophila melanogaster is not well characterized. We have studied the Drosophila orthologue of LIN52, known as dlin52, which is strongly conserved across various taxa from worms to human. dlin52 is reported to be present in a large protein complex containing important transcriptional regulators of cell proliferation and cell death like dE2F1, dMyb and dRbf. We have examined the expression of dlin52 transcripts and protein during development. Strong nuclear expression of dlin52 is seen in larval eye-antennal discs, brain, fat body, wing discs and salivary glands. dlin52 is abundantly expressed in endoreplicated tissues like salivary glands, fat body, and certain regions of the gut, and the nurse cells from adult ovaries. dlin52 is also expressed in the larval optic lobe, as well as in the developing neurons of ventral ganglion, indicating that this gene has an important role to play in cell cycle regulation and neuronal development. Robust expression of dlin52 protein was observed in quiescent cells like that of the imaginal cells of larval salivary gland, while marginal expression was seen in the germarium of adult ovary. Study of the spatial and temporal pattern of expression of this gene will help in better understanding of the function of this protein during various developmental processes. © 2011 Elsevier B.V. All rights reserved.
E3 ubiquitin ligase Deltex facilitates the expansion of Wingless gradient and antagonizes Wingless signaling through a conserved mechanism of transcriptional effector Armadillo/β-catenin degradation
(2024) Vartika Sharma; Nalani Sachan; Bappi Sarkar; Mousumi Mutsuddi; Ashim Mukherjee
The Wnt/Wg pathway controls myriads of biological phenomena throughout the development and adult life of all organisms across the phyla. Thus, an aberrant Wnt signaling is associated with a wide range of pathologies in humans. Tight regulation of Wnt/Wg signaling is required to maintain proper cellular homeostasis. Here, we report a novel role of E3 ubiquitin ligase Deltex in Wg signaling regulation. Drosophila dx genetically interacts with wg and its pathway components. Furthermore, Dx LOF results in a reduced spreading of Wg while its over-expression expands the diffusion gradient of the morphogen. We attribute this change in Wg gradient to the endocytosis of Wg through Dx which directly affects the short- and long-range Wg targets. We also demonstrate the role of Dx in regulating Wg effector Armadillo where Dx down-regulates Arm through proteasomal degradation. We also showed the conservation of Dx function in the mammalian system where DTX1 is shown to bind with β-catenin and facilitates its proteolytic degradation, spotlighting a novel step that potentially modulates Wnt/Wg signaling cascade. © 2023, Sharma et al.
Gelatin as a blocking agent in Southern blot and chromosomal in situ hybridizations
(1993) S.C. Lakhotia; Abbay Sharma; Mousumi Mutsuddi; Madhu G. Tapadia
[No abstract available]
Heat shock but not benzamide and colchicine response elements are present within the - 844 bp upstream region of the hrsω gene of Drosophila melanogaster
(Indian Academy of Sciences, 1996) S.C. Lakhotia; Mousumi Mutsuddi
The selective inducibility of hsrω gene by heat shock and several chemical agents and its selective non-inducibility by heat shock under certain conditions led to suggestion that this locus is subject to multiple controls at the level of transcription. With a view to delimit these different control elements, transgenic lines horbouring hsrω 5′ promoter deletion variants tagged to the lacZ reporter gene were used. Three different assays, viz., staining for β-galactosidase activity in different larval tissues using chromogenic X-gal substrate, [3H] uridine labelling of polytene nuclei and in situ DNA-DNA hybridization with a non-radioactive probe to polytene chrmosome spreads for checking the puffing status of the resident and the transgene in larval salivary glands, were applied to monitor the activiy of the reporter gene following different treatments. Our results showed that the -844 bp to +107 bp sequence was sufficient for heat shock induction of the transgene in all tissues. An analysis of the base sequence of the hsrω promoter revealed the presence of three consensus heat shock elements at -466, -250 and at -57 bp and of two GAGA factor binding sites at -496 and at -68bp within the -844 bp region. Germline transformants carrying the -346 bp to -844 bp region of the hsrω promoter showed only a very weak heat shock inducibility of the reporter gene in agreement with the presence of only one of the three putative heat shock elements and one of the two GAGA factor binding sites in this region. Interestingly, neither of the transformed lines (carrying the -844 bp to +107 bp or the -844 bp to -346 bp of the hsrω promoter region) showed any response of the transgene to benzamide or colchicine treatments. These results showed that while the heat shock response elements of the hsrω are included within the -844 bp region the response elements for benzamide and colchicine treatments are outside this region.
Identification and molecular characterization of two recurrent missense mutations in the RS1 gene in two families with X-linked retinoschisis from North India
(John Wiley and Sons Inc, 2023) Souradip Chatterjee; Shashank Gupta; Laxmi Kirola; Abhishek Chandra; Ashim Mukherjee; Mousumi Mutsuddi
X-linked retinoschisis (XLR) is a rare medical condition that involves in the splitting of neurosensory layers and the impairment of vision in the retina. In majority of the XLR cases, pathogenic variants in Retinoschisin 1 (RS1) gene have been implicated in males with an early age of onset during early childhood. In the present study, we have recruited two North Indian families having multiple affected male members, who were diagnosed with XLR. The entire protein-coding region of RS1 was screened by PCR-Sanger sequencing and two recurrent pathogenic variants (p.I81N and p.R102Q) were unraveled. The in vitro study of these variants demonstrated the aggregation of mutant RS1 within the endoplasmic reticulum. Furthermore, mutant forms of this protein showed significant intracellular retention, which was evident by the absence of retinoschisin protein fractions in the extracellular media. These inferences were also supported by extensive bioinformatics analysis of the mutants, which showed dramatic conformational changes in the local structure of retinoschisin. Thus, our study suggests that the identified pathogenic variants interfere with proper protein folding, leading to anomalous structural changes ultimately resulting in intracellular retention of retinoschisin within the retina. © 2023 Wiley Periodicals LLC.
In vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster model relate with therapeutic applications
(2012) Vibha Dwivedi; E.M. Anandan; Rajesh S. Mony; T.S. Muraleedharan; M.S. Valiathan; Mousumi Mutsuddi; Subhash C. Lakhotia
Background: Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their "active" components as is done in most current studies. Methods: We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative) and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury), for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP) levels of Drosophila melanogaster using at least 200 larvae or flies for each assay. Results: A 0.5% (weight/volume) supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity. Conclusions: The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular bases of the effects of different Ayurvedic formulations. © 2012 Dwivedi et al.
Insights into human neurodegeneration: Lessons learnt from drosophila
(Springer Singapore, 2019) Mousumi Mutsuddi; Ashim Mukherjee
This book is aimed at generating an updated reservoir of scientific endeavors undertaken to unravel the complicated yet intriguing topic of neurodegeneration. Scientists from Europe, USA and India who are experts in the field of neurodegenerative diseases have contributed to this book. This book will help readers gain insight into the recent knowledge obtained from Drosophila model, in understanding the molecular mechanisms underlying neurodegenerative disorders and also unravel novel scopes for therapeutic interventions. Different methodologies available to create humanized fly models that faithfully reflects the pathogenicities associated with particular disorders have been described here. It also includes information on the exciting area of neural stem cells. A brief discussion on neurofibrillary tangles, precedes the elaborate description of lessons learnt from Drosophila about Alzheimer’s, Parkinson’s, Spinomuscular Atrophy, Huntington’s diseases, RNA expansion disorders and Hereditary Spastic Paraplegia. We have concluded the book with the use of Drosophila for identifying pharmacological therapies for neurodegenerative disorders. The wide range of topics covered here will not only be relevant for beginners who are new to the concept of the extensive utility of Drosophila as a model to study human disorders; but will also be an important contribution to the scientific community, with an insight into the paradigm shift in our understanding of neurodegenerative disorders. Completed with informative tables and communicative illustrations this book will keep the readers glued and intrigued. We have comprehensively anthologized the lessons learnt on neurodegeneration from Drosophila and have thus provided an insight into the multidimensional aspects of pathogenicities of majority of the neurodegenerative disorders. © Springer Nature Singapore Pte Ltd. 2019.
Interaction of Spoonbill with Prospero in Drosophila: Implications in neuroblast development
(John Wiley and Sons Inc., 2017) Bipin K. Tripathi; Rituparna Das; Ashim Mukherjee; Mousumi Mutsuddi
Identification of Spoon as a suppressor of SCA8 associated neurodegeneration provides us a hint about its role in neuronal development and maintenance. However, a detailed molecular characterization of spoon has not yet been reported. Here, we describe spatial expression pattern of Spoon during Drosophila development. Quantitative real time-PCR and fluorescent RNA–RNA in situ hybridization indicate that Spoon is expressed at relatively high levels in larval brain and photoreceptors of eye-antennal discs. Immunostaining reveals that Spoon is subcellularly localized in the cytoplasm and is also membrane bound. Strong expression is also seen in adult ovary and testes. Spoon on immunostaining exhibits unique pattern of expression in larval brain. We observed that Spoon in the neuroblasts colocalizes with Prospero, a transcription factor regulating genes involved in neuroblast self-renewal or cell-cycle control. Co-immunoprecipitation suggests that Spoon and Prospero reside in the same protein complex. Using Drosophila model of SCA8 RNA neuropathy we have also shown that loss of Prospero hinders the suppression of SCA8 associated neurodegeneration by Spoonbill, suggesting Prospero and Spoon might genetically interact and function together. Our study presents Spoon as a novel interacting partner of Prospero and this might be critical in determining the polarized localization of cell fate determinants. © 2017 Wiley Periodicals, Inc.
Kinase active Misshapen regulates Notch signaling in Drosophila melanogaster
(Academic Press Inc., 2015) Abhinava K. Mishra; Nalani Sachan; Mousumi Mutsuddi; Ashim Mukherjee
Notch signaling pathway represents a principal cellular communication system that plays a pivotal role during development of metazoans. Drosophila misshapen (msn) encodes a protein kinase, which is related to the budding yeast Ste20p (sterile 20 protein) kinase. In a genetic screen, using candidate gene approach to identify novel kinases involved in Notch signaling, we identified msn as a novel regulator of Notch signaling. Data presented here suggest that overexpression of kinase active form of Msn exhibits phenotypes similar to Notch loss-of-function condition and msn genetically interacts with components of Notch signaling pathway. Kinase active form of Msn associates with Notch receptor and regulate its signaling activity. We further show that kinase active Misshapen leads to accumulation of membrane-tethered form of Notch. Moreover, activated Msn also depletes Armadillo and DE-Cadherin from adherens junctions. Thus, this study provides a yet unknown mode of regulation of Notch signaling by Misshapen. © 2015 Elsevier Inc.
Maheshvara regulates JAK/STAT signaling by interacting and stabilizing hopscotch transcripts which leads to apoptosis in Drosophila melanogaster
(Springer Nature, 2021) Bhawana Maurya; Satya Surabhi; Rituparna Das; Pranjali Pandey; Ashim Mukherjee; Mousumi Mutsuddi
Maheshvara (mahe), an RNA helicase that is widely conserved across taxa, regulates Notch signaling and neuronal development in Drosophila. In order to identify novel components regulated by mahe, transcriptome profiling of ectopic mahe was carried out and this revealed striking upregulation of JAK/STAT pathway components like upd1, upd2, upd3, and socs36E. Further, significant downregulation of the pathway components in mahe loss-of-function mutant as well as upon lowering the level of mahe by RNAi, supported and strengthened our transcriptome data. Parallelly, we observed that mahe, induced caspase-dependent apoptosis in photoreceptor neurons, and this phenotype was significantly modulated by JAK/STAT pathway components. RNA immunoprecipitation unveiled the presence of JAK/STAT tyrosine kinase hopscotch (hop) transcripts in the complex immunoprecipitated with Mahe, which ultimately resulted in stabilization and elevation of hop transcripts. Additionally, we also observed the surge in activity of downstream transcription factor Stat92E, which is indicative of activation of the JAK/STAT signaling, and this in turn led to apoptosis via upregulation of hid. Taken together, our data provide a novel regulation of JAK/STAT pathway by RNA helicase Maheshvara, which ultimately promotes apoptosis. © 2021, The Author(s).