Brain defects often lead to motor dysfunctions in humans. Drosophila melanogaster has been one of the most useful organisms in the study of neuronal biology due to its similarities with humans and has contributed to a more detailed understanding of the effects of genetic dysfunctions in the brain on behavior. We herein present modified protocols for the crawling assay with larvae and the climbing assay with adult flies that are simple to perform as well as a series of commands for ImageJ to automatically analyze data for the crawling assay.
View Article and Find Full Text PDFBiochem Biophys Res Commun
November 2021
Neuron-restrictive silencing factor (NRSF), also known as RE-1 silencing transcription factor (REST), has pivotal functions in many neuron-specific genes. Previous studies revealed that neuron-specific alternative splicing (AS) of REST produces divergent forms of REST variants and provides regulatory complexity in the nervous system. However, the biological significance of these variants in the regulation of neuronal activities remains to be clarified.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most epidemic neuronal dysfunctions among elderly people. It is accompanied by neuronal disorders along with learning and memory defects, as well as massive neurodegeneration phenotype. The presence of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques, called senile plaques (SPs), and brain atrophy are typically observed in the brains of AD patients.
View Article and Find Full Text PDFThe assembly and deposition of amyloid β protein (Aβ) is a fundamental event during the early stages of Alzheimer's disease (AD) and cerebral amyloid angiopathy. A growing body of evidence indicates that gangliosides form a pathological platform for the generation of ganglioside-bound Aβ, which facilitates the assembly of soluble Aβs; however, the molecular mechanisms underlying the binding of Aβ to gangliosides in the brain remain unclear due to the lack of an in vivo system that may address this issue. In insects, including the fruit fly Drosophila melanogaster, gangliosides are not intrinsically present at a detectable level.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly. During the progression of AD, massive neuronal degeneration occurs in the late stage of the disease; however, the molecular mechanisms responsible for this neuronal loss remain unknown. AβpE3-42 (an N-terminal-truncated amyloid-β peptide that begins with pyroglutamate at the third position) is produced during late-stage AD.
View Article and Find Full Text PDFActa Neuropathol Commun
October 2016
Several species of β-amyloid peptides (Aβ) exist as a result of differential cleavage from amyloid precursor protein (APP) to yield various C-terminal Aβ peptides. Several N-terminal modified Aβ peptides have also been identified in Alzheimer's disease (AD) brains, the most common of which is pyroglutamate-modified Aβ (Aβ). Aβ peptide has an increased propensity to aggregate, appears to accumulate in the brain before the appearance of clinical symptoms of AD, and precedes Aβ deposition.
View Article and Find Full Text PDFTransducin β-like 1 (TBL1), a transcriptional co-repressor complex, is a causative factor for late-onset hearing impairments. Transcriptional co-repressor complexes play pivotal roles in gene expression by making a complex with divergent transcription factors. However, it remained to be clarified how co-repressor complex regulates cellular survival.
View Article and Find Full Text PDFIncreasing evidence indicates that defects in the sensory system are highly correlated with age-related neurodegenerative diseases, including Alzheimer's disease (AD). This raises the possibility that sensory cells possess some commonalities with neurons and may provide a tool for studying AD. The sensory system, especially the auditory system, has the advantage that depression in function over time can easily be measured with electrophysiological methods.
View Article and Find Full Text PDFThe innate immune response and stress-induced apoptosis are well-established signaling pathways related to cellular defense. NF-κB and AP-1 are redox-sensitive transcription factors that play important roles in those pathways. Here we show that Ebi, a Drosophila homolog of the mammalian co-repressor molecule transducin β-like 1 (TBL1), variously regulates the expression of specific genes that are targets of redox-sensitive transcription factors.
View Article and Find Full Text PDFMethylene blue (MB) inhibits the aggregation of tau, a main constituent of neurofibrillary tangles. However, MB's mode of action in vivo is not fully understood. MB treatment reduced the amount of sarkosyl-insoluble tau in Drosophila that express human wild-type tau.
View Article and Find Full Text PDFAging is a major risk factor for Alzheimer's disease (AD). Aggregation of amyloid beta (Aβ) in cerebral cortex and hippocampus is a hallmark of AD. Many factors have been identified as causative elements for onset and progression of AD; for instance, tau seems to mediate the neuronal toxicity of Aβ, and downregulation of macroautophagy (autophagy) is thought to be a causative element of AD pathology.
View Article and Find Full Text PDFIntestinal stem cells (ISCs) in the adult Drosophila midgut can respond to tissue damage and support repair. We used genetic manipulation to increase the number of ISC-like cells in the adult midgut and performed gene expression profiling to identify potential ISC regulators. A detailed analysis of one of these potential regulators, the zinc-finger protein Charlatan, was carried out.
View Article and Find Full Text PDFDev Growth Differ
June 2014
Neuronal network consists of many types of neuron and glial cells. This diversity is guaranteed by the constant cell proliferation of neuronal stem cells following stop cell cycle re-entry, which leads to differentiation during development. Neuronal differentiation occurs mainly at the specific cell cycle phase, the G1 phase.
View Article and Find Full Text PDFAs multicellular organisms develop, many cells permanently stop dividing and undergo terminal differentiation. The G1 phase of the cell cycle is thought to be the critical decision point for differentiation. Many growth factors, such as epidermal growth factor, are involved in regulating the G1 to S phase transition, and aberrant activation of growth factor signaling is one of the critical causes of tumor formation.
View Article and Find Full Text PDFThe IMD pathway is one of the major regulators of the innate immune response in Drosophila. Although extensive analysis of the IMD pathway has been carried out, precise mechanisms for how each target gene of the pathway is down-regulated remain to be clarified. Here, we carried out genetic screening and found that fat facets (faf), which encodes a deubiquitinating enzyme, inhibited the expression of the target genes of the IMD pathway.
View Article and Find Full Text PDFSensory organs are constantly exposed to physical and chemical stresses that collectively threaten the survival of sensory neurons. Failure to protect stressed neurons leads to age-related loss of neurons and sensory dysfunction in organs in which the supply of new sensory neurons is limited, such as the human auditory system. Transducin β-like protein 1 (TBL1) is a candidate gene for ocular albinism with late-onset sensorineural deafness, a form of X-linked age-related hearing loss.
View Article and Find Full Text PDFThe O-type forkhead domain transcription factor (FOXO) is involved in many biological processes such as aging, the oxidative stress response, and growth regulation. FOXO activity is tightly controlled within cells. In particular, growth factor signaling pathways and the oxidative stress response can both stimulate nuclear translocation of this transcription factor.
View Article and Find Full Text PDFSensory bristle formation in Drosophila is a well-characterized system for studying sensory organ development at the molecular level. The master proneural genes of the achaete-scute (ac-sc) complex, which encode basic-helix-loop-helix (bHLH) transcription factors, are necessary and sufficient for sensory bristle formation. charlatan (chn) was originally identified as a transcriptional activator of ac-sc gene expression through interaction with its enhancer, an activity that promotes sensory bristle development.
View Article and Find Full Text PDFThe downregulation of E-cadherin by Src promotes epithelial to mesenchymal transition and tumorigenesis. However, a simple loss of cell adhesion is not sufficient to explain the diverse developmental roles of Src and metastatic behavior of viral Src-transformed cells. Here, we studied the functions of endogenous and activated forms of Drosophila Src in the context of tracheal epithelial development, during which extensive remodeling of adherens junctions takes place.
View Article and Find Full Text PDFAllelic mutants exhibiting growth defects in Drosophila were isolated. Molecular cloning identified the responsible gene as a budding yeast Tim50 ortholog, and thus it was named tiny tim 50 (ttm50). The weak allele (ttm50(Gp99)) produced small flies due to reduced cell size and number, and growth terminated at the larval stage in the strong alleles (ttm50(IE1) and ttm50(IE2)).
View Article and Find Full Text PDFThe corepressor complex that includes Ebi and SMRTER is a target of epidermal growth factor (EGF) and Notch signaling pathways and regulates Delta (Dl)-mediated induction of support cells adjacent to photoreceptor neurons of the Drosophila eye. We describe a mechanism by which the Ebi/SMRTER corepressor complex maintains Dl expression. We identified a gene, charlatan (chn), which encodes a C2H2-type zinc-finger protein resembling human neuronal restricted silencing factor/repressor element RE-1 silencing transcription factor (NRSF/REST).
View Article and Find Full Text PDFBackground: Ligand-induced proteolytic cleavage and internalization of the plasma membrane receptor Notch leads to its activation. Ligand-independent, steady-state internalization of Notch, however, does not lead to activation. The mechanism by which downstream effectors discriminate between these bipartite modes of Notch internalization is not understood.
View Article and Find Full Text PDFBiochem Biophys Res Commun
November 2003
Neural precursor cells actively proliferate in the ventricular zone to self-renew the stem cell population, and in parallel, maintain their undifferentiated state. This progenitor pool generates postmitotic cells that migrate to the mantle layer and differentiate into mature neurons. The growth of these stem cells is strictly controlled by the canonical Wnt signaling cascade, in part mediated by the direct regulation of Cyclin D1, a critical regulator of cell cycle progression.
View Article and Find Full Text PDFThe Notch and Epidermal Growth Factor Receptor (EGFR) pathways both regulate proliferation and differentiation, and the cellular response to each is often influenced by the other. Here, we describe a mechanism that links them in a sequential fashion, in the developing compound eye of Drosophila. EGFR activation induces photoreceptor (R cell) differentiation and promotes their expression of Delta.
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