@article {683, title = {Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS.}, journal = {PLoS Genet}, volume = {13}, year = {2017}, month = {2017 Oct}, pages = {e1007043}, abstract = {

Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are important for the maintenance of the activity of the enhancer rather than its initiation. We also find that Exd function is independent of its known partner homothorax in this apoptosis. We extend some of our findings to Deformed expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox dependent apoptosis. We propose a mechanism where common players like Exd-Grh-Notch work with different Hox genes through region specific enhancers to pattern respective segments of larval central nervous system.

}, keywords = {Amino Acid Sequence, Animals, Apoptosis, Central Nervous System, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Developmental, Genes, Homeobox, Homeodomain Proteins, Larva, Male, Nuclear Proteins, Receptors, Notch, Transcription Factors}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1007043}, author = {Khandelwal, Risha and Sipani, Rashmi and Govinda Rajan, Sriivatsan and Kumar, Raviranjan and Joshi, Rohit} } @article {476, title = {The E3 ligase ube3a is required for learning in Drosophila melanogaster. [Drosophila facility]}, journal = {Biochem Biophys Res Commun}, volume = {462}, year = {2015}, month = {2015 Jun 19}, pages = {71-7}, abstract = {

Angelman syndrome and autism are neurodevelopmental disorders linked to mutations and duplications of an E3 ligase called ube3a respectively. Since cognitive deficits and learning disabilities are hallmark symptoms of both these disorders, we investigated a role for dube3a in the learning ability of flies using the aversive phototaxis suppression assay. We show that down and up-regulation of dube3a are both detrimental to learning in larvae and adults. Using conditional gene expression we found that dube3a is required for normal brain development and during adulthood. Furthermore, we suggest that dube3a could be interacting with other learning and memory genes such as derailed. Along with firmly establishing dube3a as a gene that is required for learning, our work also opens avenues for further understanding the role played by this gene in brain development and behavior.

}, keywords = {Animals, Animals, Genetically Modified, Brain, Drosophila melanogaster, Drosophila Proteins, Gene Expression Regulation, Developmental, Immunoblotting, Larva, Learning, Memory, Motor Activity, Mushroom Bodies, Mutation, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Ubiquitin-Protein Ligases}, issn = {1090-2104}, doi = {10.1016/j.bbrc.2015.04.110}, author = {Chakraborty, Moumita and Paul, Blesson K and Nayak, Tanmoyita and Das, Aniruddha and Jana, Nihar R and Bhutani, Supriya} } @article {478, title = {Functional implementation of Drosophila itpr mutants by rat Itpr1. [Drosophila facility]}, journal = {J Neurogenet}, volume = {26}, year = {2012}, month = {2012 Sep}, pages = {328-37}, abstract = {

The Drosophila inositol 1,4,5-trisphosphate receptor (IP(3)R) and mammalian type-1 IP(3)Rs have 57-60\% sequence similarity and share major domain homology with each other. Mutants in the single Drosophila IP(3)R gene, itpr, and Itpr1 knockout mice both exhibit lethality and defects in motor coordination. Here the authors show that the rat type-1 IP(3)R, which is the major neuronal isoform, when expressed in the pan-neuronal domain in Drosophila, functionally complements Drosophila IP(3)R function at cellular and systemic levels. It rescues the established neuronal phenotypes of itpr mutants in Drosophila, including wing posture, flight, electrophysiological correlates of flight maintenance, and intracellular calcium dynamics. This is the first in vivo demonstration of functional homology between a mammalian and fly IP(3)R. This study also paves the way for cellular and molecular analyses of the spinocerebellar ataxias in Drosophila, since SCA15/16 is known to be caused by heterozygosity of human ITPR1.

}, keywords = {Animals, Animals, Genetically Modified, Calcium, Cells, Cultured, Cytosol, Drosophila, Drosophila Proteins, Flight, Animal, Gene Expression Regulation, Genetic Therapy, Inositol 1,4,5-Trisphosphate Receptors, Larva, Movement Disorders, Mutation, Neurons, Physical Stimulation, Rats, Transcription Factors, Wings, Animal}, issn = {1563-5260}, doi = {10.3109/01677063.2012.697501}, author = {Chakraborty, Sumita and Hasan, Gaiti} } @article {479, title = {Interaction with a kinesin-2 tail propels choline acetyltransferase flow towards synapse. [Drosophila facility]}, journal = {Traffic}, volume = {13}, year = {2012}, month = {2012 Jul}, pages = {979-91}, abstract = {

Bulk flow constitutes a substantial part of the slow transport of soluble proteins in axons. Though the underlying mechanism is unclear, evidences indicate that intermittent, kinesin-based movement of large protein-aggregates aids this process. Choline acetyltransferase (ChAT), a soluble enzyme catalyzing acetylcholine synthesis, propagates toward the synapse at an intermediate, slow rate. The presynaptic enrichment of ChAT requires heterotrimeric kinesin-2, comprising KLP64D, KLP68D and DmKAP, in Drosophila. Here, we show that the bulk flow of a recombinant Green Fluorescent Protein-tagged ChAT (GFP::ChAT), in Drosophila axons, lacks particulate features. It occurs for a brief period during the larval stages. In addition, both the endogenous ChAT and GFP::ChAT directly bind to the KLP64D tail, which is essential for the GFP::ChAT entry and anterograde flow in axon. These evidences suggest that a direct interaction with motor proteins could regulate the bulk flow of soluble proteins, and thus establish their asymmetric distribution.

}, keywords = {Animals, Animals, Genetically Modified, Axonal Transport, Carrier Proteins, Choline O-Acetyltransferase, Cholinergic Neurons, Drosophila, Drosophila Proteins, Fluorescence Recovery After Photobleaching, Kinesin, Larva, Microtubule-Associated Proteins, Protein Interaction Domains and Motifs, Synapses}, issn = {1600-0854}, doi = {10.1111/j.1600-0854.2012.01361.x}, author = {Sadananda, Aparna and Hamid, Runa and Doodhi, Harinath and Ghosal, Debnath and Girotra, Mukul and Jana, Swadhin Chandra and Ray, Krishanu} } @article {721, title = {Synaptic activity in serotonergic neurons is required for air-puff stimulated flight in Drosophila melanogaster.}, journal = {PLoS One}, volume = {7}, year = {2012}, month = {2012}, pages = {e46405}, abstract = {

BACKGROUND: Flight is an integral component of many complex behavioral patterns in insects. The giant fiber circuit has been well studied in several insects including Drosophila. However, components of the insect flight circuit that respond to an air-puff stimulus and comprise the flight central pattern generator are poorly defined. Aminergic neurons have been implicated in locust, moth and Drosophila flight. Here we have investigated the requirement of neuronal activity in serotonergic neurons, during development and in adults, on air-puff induced flight in Drosophila.

METHODOLOGY/PRINCIPAL FINDINGS: To target serotonergic neurons specifically, a Drosophila strain that contains regulatory regions from the TRH (Tryptophan Hydroxylase) gene linked to the yeast transcription factor GAL4 was used. By blocking synaptic transmission from serotonergic neurons with a tetanus toxin transgene or by hyperpolarisation with Kir2.1, close to 50\% adults became flightless. Temporal expression of a temperature sensitive Dynamin mutant transgene (Shi(ts)) suggests that synaptic function in serotonergic neurons is required both during development and in adults. Depletion of IP(3)R in serotonergic neurons via RNAi did not affect flight. Interestingly, at all stages a partial requirement for synaptic activity in serotonergic neurons was observed. The status of serotonergic neurons was investigated in the central nervous system of larvae and adults expressing tetanus toxin. A small but significant reduction was observed in serotonergic cell number in adult second thoracic segments from flightless tetanus toxin expressing animals.

CONCLUSIONS: These studies show that loss of synaptic activity in serotonergic neurons causes a flight deficit. The temporal focus of the flight deficit is during pupal development and in adults. The cause of the flight deficit is likely to be loss of neurons and reduced synaptic function. Based on the partial phenotypes, serotonergic neurons appear to be modulatory, rather than an intrinsic part of the flight circuit.

}, keywords = {Animals, Cell Count, Central Nervous System, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Dynamins, Flight, Animal, Gene Expression Regulation, Developmental, Larva, Potassium Channels, Inwardly Rectifying, Pupa, Saccharomyces cerevisiae Proteins, Serotonergic Neurons, Synaptic Transmission, Tetanus Toxin, Transcription Factors, Transgenes, Tryptophan Hydroxylase}, issn = {1932-6203}, doi = {10.1371/journal.pone.0046405}, author = {Sadaf, Sufia and Birman, Serge and Hasan, Gaiti} }