Hikaru genki protein is secreted into synaptic clefts from an early stage of synapse formation in Drosophila

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 589-597 ◽  
Author(s):  
M. Hoshino ◽  
E. Suzuki ◽  
Y. Nabeshima ◽  
C. Hama
Keyword(s):  
Critical Period ◽  
Synapse Formation ◽  
Neural Circuits ◽  
Motor Behavior ◽  
Early Stage ◽  
Axon Growth ◽  
Number Of Factors ◽  
Protein Functions ◽  
Abnormal Motor ◽  
Immunohistochemical Analyses

The development of neural circuits is regulated by a large number of factors that are localized at distinct neural sites. We report here the localization of one of these factors, hikaru genki (hig) protein, at synaptic clefts in the pupal and adult nervous systems of Drosophila. In hig mutants, unusually frequent bursting activity of the muscles and abnormal motor behavior during the adult stage suggest the misfunction of neuromuscular circuitry. Our immunohistochemical analyses revealed that hig protein, produced by neurons, is secreted from the presynaptic terminals into the spaces between the presynaptic and postsynaptic terminals. In addition, we have found that the localization of this protein in the synaptic spaces temporally correlates with its functional requirement during a critical period that occurs in the middle stage of pupal formation, a period when a number of dendrite and axon growth cones meet to form synapses. These findings indicate that hig protein functions in the formation of functional neural circuits from the early stages of synapse formation.

scholarly journals Molecular Mechanisms Underlying Activity-Dependent GABAergic Synapse Development and Plasticity and Its Implications for Neurodevelopmental Disorders

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Bidisha Chattopadhyaya
Keyword(s):  
Neurodevelopmental Disorders ◽  
Critical Period ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Neural Circuits ◽  
Normal Function ◽  
Gabaergic Synapse ◽  
Synapse Maturation ◽  
Circuit Development ◽  
Activity Dependent

GABAergic interneurons are critical for the normal function and development of neural circuits, and their dysfunction is implicated in a large number of neurodevelopmental disorders. Experience and activity-dependent mechanisms play an important role in GABAergic circuit development, also recent studies involve a number of molecular players involved in the process. Emphasizing the molecular mechanisms of GABAergic synapse formation, in particular basket cell perisomatic synapses, this paper draws attention to the links between critical period plasticity, GABAergic synapse maturation, and the consequences of its dysfunction on the development of the nervous system.

scholarly journals Anosognosia in People with Cognitive Impairment: Association with Cognitive Deficits and Behavioral Disturbances

2015 ◽  
Vol 5 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Antonella De Carolis ◽  
Virginia Cipollini ◽  
Valentina Corigliano ◽  
Anna Comparelli ◽  
Micaela Sepe-Monti ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Rating Scale ◽  
Motor Behavior ◽  
Psychiatric Symptoms ◽  
Early Stage ◽  
Functional Anatomy ◽  
Night Time ◽  
Behavioral Disturbances ◽  
The Relationship

Aims: To investigate, in a group of subjects at an early stage of cognitive impairment, the relationship between anosognosia and both cognitive and behavioral symptoms by exploring the various domains of insight. Methods: One hundred and eight subjects affected by cognitive impairment were consecutively enrolled. The level of awareness was evaluated by means of the Clinical Insight Rating Scale (CIRS). Psychiatric symptoms were evaluated using the Italian version of the Neuropsychiatric Inventory (NPI), whereas memory (memory index, MI) and executive (executive index, EI) functions were explored using a battery of neuropsychological tests and qualified by means of a single composite cognitive index score for each function. Results: A significant positive correlation between the total NPI score and global anosognosia score was found. Furthermore, both the MI and EI scores were lower in subjects with anosognosia than in those without anosognosia (p < 0.001 and p < 0.007, respectively). When the single domains of the CIRS were considered, anosognosia of reason of visit correlated with the EI score (r = -0.327, p = 0.01) and night-time behavioral disturbances (r = 0.225; p = 0.021); anosognosia of cognitive deficit correlated with depression (r = -0.193; p = 0.049) and the MI score (r = -0.201; p = 0.040); anosognosia of functional deficit correlated with the MI score (r = -0.257; p = 0.008), delusions (r = 0.232; p = 0.015) and aberrant motor behavior (r = 0.289; p = 0.003); anosognosia of disease progression correlated with the MI score (r = -0.236; p = 0.015), agitation (r = 0.247; p = 0.011), aberrant motor behavior (r = 0.351; p = 0.001) and night-time behavioral disturbances (r = 0.216; p = 0.027). Conclusions: Our study suggests that, in the early stage of cognitive impairment, anosognosia is associated with both cognitive deficits and behavioral disorders according to the specific functional anatomy of the symptoms.

scholarly journals MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development

2020 ◽  
Author(s):  
Guillermo E. Parada ◽  
Roberto Munita ◽  
Ilias Georgakopoulos-Soares ◽  
Hugo Fernandez ◽  
Emmanouil Metzakopian ◽  
...  
Keyword(s):  
Neuronal Development ◽  
Synapse Formation ◽  
De Novo ◽  
Axon Growth ◽  
Developmental Time ◽  
Rna Seq ◽  
Mouse Tissues ◽  
Comprehensive Survey ◽  
Mouse Transcript ◽  
Mouse Visual Cortex

AbstractMicroexons, exons that are ≤30 nucleotides, were shown to play key roles in neuronal development, but are difficult to detect and quantify using standard RNA-Seq alignment tools. Here, we present MicroExonator, a novel pipeline for reproducible de novo discovery and quantification of microexons. We processed 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mouse. We detected 2,984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons alone segregates brain tissues by developmental time and further analysis suggest a key function for microexon inclusion in axon growth and synapse formation. Finally, we analysed single-cell RNA-seq data from the mouse visual cortex and we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell-type specific.

scholarly journals The Role and Mechanism of AMIGO3 in the Formation of Aberrant Neural Circuits After Status Convulsion in Immature Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Xue Li ◽  
Yanan Pan ◽  
Jianxiong Gui ◽  
Zhixu Fang ◽  
Dishu Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Axonal Regeneration ◽  
Neural Circuits ◽  
Axon Growth ◽  
Demyelinating Diseases ◽  
Reading Frame ◽  
Myelin Sheaths ◽  
Transmission Electron ◽  
Rhoa Signaling ◽  
Myelin Basic Protein Expression

Leucine rich repeat and immunoglobulin-like domain-containing protein 1 (Lingo-1) has gained considerable interest as a potential therapy for demyelinating diseases since it inhibits axonal regeneration and myelin production. However, the results of clinical trials targeted at Lingo-1 have been unsatisfactory. Amphoterin-induced gene and open reading frame-3 (AMIGO3), which is an analog of Lingo-1, might be an alternative therapeutic target for brain damage. In the present study, we investigated the effects of AMIGO3 on neural circuits in immature mice after status convulsion (SC) induced by kainic acid. The expression of both AMIGO3 and Lingo-1 was significantly increased after SC, with levels maintained to 20 days after SC. Following SC, transmission electron microscopy revealed the impaired microstructure of myelin sheaths and Western blot analysis showed a decrease in myelin basic protein expression, and this damage was alleviated by downregulation of AMIGO3 expression. The ROCK/RhoA signaling pathway was inhibited at 20 days after SC by downregulating AMIGO3 expression. These results indicate that AMIGO3 plays important roles in seizure-induced damage of myelin sheaths as well as axon growth and synaptic plasticity via the ROCK/RhoA signaling pathway.

A critical period for the impact of vestibular sensation on ferret motor development

2007 ◽  
Vol 16 (4-5) ◽  
pp. 179-186
Author(s):  
S. Van Cleave ◽  
M.S. Shall
Keyword(s):  
Vestibular System ◽  
Motor Development ◽  
Critical Period ◽  
Motor Behavior ◽  
Fiber Development ◽  
Type I ◽  
Behavior Development ◽  
Sham Surgery ◽  
Walking Balance ◽  
The Impact

Children with hearing deficits and hypofunctioning vestibular receptors frequently have delayed motor development. This study focuses on when the vestibular system needs to be active for normal motor behavior development and the maturation of the soleus muscle in the ferret. Both vestibular labyrinths were removed from ferrets at Postnatal day 10 (P10), P21, or P45 and the resulting data were compared with ferrets that had undergone a sham surgery at the same ages. The animals were sacrificed at P120 (young adult ferret). The resulting data from these ferrets revealed that standing and walking balance was significantly affected when the vestibular system was eliminated at or before P21. The soleus of P10 and P21 animals generally had smaller diameter muscle fibers and proportionally less type I Myosin Heavy Chain (MHC) and more type IIX MHC. The twitch contraction time of the soleus of the P21 group was significantly slower than the other groups. It appears that the vestibular system is important to motor and muscle fiber development in the ferret during the period before P21. The eyes are still closed at that age and all of the vestibular receptors are not fully mature. These findings imply a "critical period" for vestibular sensation and the development of a muscle that is important to standing balance.

Emerging roles for HOX proteins in synaptogenesis

2018 ◽  
Vol 62 (11-12) ◽  
pp. 807-818 ◽  
Author(s):  
Françoise Gofflot ◽  
Benoit Lizen
Keyword(s):  
Cell Fate ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Target Selection ◽  
Axon Growth ◽  
Current Data ◽  
Cell Fate Specification ◽  
Hox Proteins ◽  
Circuit Formation ◽  
Vertebrate Central Nervous System

Neural circuit formation requires the intricate orchestration of multiple developmental events including cell fate specification, cell migration, axon guidance, dendritic growth, synaptic target selection, and synaptogenesis. The HOX proteins are well-known transcriptional regulators that control embryonic development. Investigations into their action in the vertebrate central nervous system have demonstrated pivotal roles in specifying neural subpopulations, but also in several successive steps required for the assembly of neuronal circuitry, such as neuron migration, axon growth and pathfinding and synaptic target selection. Several lines of evidence suggest that the HOX transcription factors could also regulate synaptogenesis processes even after the process of axonal and dendritic guidance has concluded. Here we will review the current data on HOX proteins in neural circuit formation in order to evaluate their potential roles in establishing neuronal connectivity with specific emphasis on synapse formation and maturation.

Perturbation of mammalian cell division: human mini segregants derived from mitotic cells

1975 ◽  
Vol 189 (1097) ◽  
pp. 591-602 ◽  
Keyword(s):  
Early Stage ◽  
Parental Cell ◽  
Optimal Conditions ◽  
Thiol Compounds ◽  
Number Of Factors ◽  
Wide Range ◽  
And Storage ◽  
Dense Chromatin ◽  
Size And Structure ◽  
Mitotic Cells

Mitotic HeLa cells can be induced to undergo abnormal cleavage and to give rise thereby to clusters of buds and/or to free mini segregants. A wide range of morphologies can be produced and the mini segregants vary considerably in size and structure. Some contain DNA which may or may not be enclosed in a nuclear membrane. This DNA in some of the mini segregants originates from dense ‘chromatin bodies’ which migrate to the periphery of the parental cell at an early stage of mitotic perturbation. The percentage of mitotic cells which undergo abnormal cleavage is affected by a number of factors including the pH of the medium, the presence of dithiothreitol or certain other thiol compounds, the absence of serum and storage of the mitotic cells at 4 °C before treatment. To date, the optimal conditions are: incubation at 37 °C in Hanks solution buffered at pH 8.0–8.4, after storage of the mitotic cells for about 3 h at 4 °C. Under these conditions about 70 % of the total mitotic population undergoes abnormal cleavage to produce clusters of mini segregants in the course of an incubation period of 3½ h. Possible mechanisms underlying the phenomenon are discussed.

scholarly journals Circulating Cell-Free Tumour DNA for Early Detection of Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3704
Author(s):  
Jedrzej J. Jaworski ◽  
Robert D. Morgan ◽  
Shivan Sivakumar
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Early Stage ◽  
Lower Sensitivity ◽  
Detection Rates ◽  
Early Stage Disease ◽  
Genetic Sequencing ◽  
Number Of Factors ◽  
Stage Disease ◽  
Invasive Method

Pancreatic cancer is a lethal disease, with mortality rates negatively associated with the stage at which the disease is detected. Early detection is therefore critical to improving survival outcomes. A recent focus of research for early detection is the use of circulating cell-free tumour DNA (ctDNA). The detection of ctDNA offers potential as a relatively non-invasive method of diagnosing pancreatic cancer by using genetic sequencing technology to detect tumour-specific mutational signatures in blood samples before symptoms manifest. These technologies are limited by a number of factors that lower sensitivity and specificity, including low levels of detectable ctDNA in early stage disease and contamination with non-cancer circulating cell-free DNA. However, genetic and epigenetic analysis of ctDNA in combination with other standard diagnostic tests may improve early detection rates. In this review, we evaluate the genetic and epigenetic methods under investigation in diagnosing pancreatic cancer and provide a perspective for future developments.

scholarly journals The Level of AdpA Directly Affects Expression of Developmental Genes in Streptomyces coelicolor

2011 ◽  
Vol 193 (22) ◽  
pp. 6358-6365 ◽  
Author(s):  
Marcin Wolański ◽  
Rafał Donczew ◽  
Agnieszka Kois-Ostrowska ◽  
Paweł Masiewicz ◽  
Dagmara Jakimowicz ◽  
...  
Keyword(s):  
Early Stage ◽  
Response Regulator ◽  
Streptomyces Coelicolor ◽  
Streptomyces Griseus ◽  
Morphological Differentiation ◽  
Aerial Mycelium ◽  
Content Type ◽  
Protein Functions

AdpA is a key regulator of morphological differentiation inStreptomyces. In contrast toStreptomyces griseus, relatively little is known about AdpA protein functions inStreptomyces coelicolor. Here, we report for the first time the translation accumulation profile of theS. coelicoloradpA(adpASc) gene; the level ofS. coelicolorAdpA (AdpASc) increased, reaching a maximum in the early stage of aerial mycelium formation (after 36 h), and remained relatively stable for the next several hours (48 to 60 h), and then the signal intensity decreased considerably. AdpAScspecifically binds theadpAScpromoter regionin vitroandin vivo, suggesting that its expression is autoregulated; surprisingly, in contrast toS. griseus, the protein presumably acts as a transcriptional activator. We also demonstrate a direct influence of AdpAScon the expression of several genes whose products play key roles in the differentiation ofS. coelicolor: STI, a protease inhibitor; RamR, an atypical response regulator that itself activates expression of the genes for a small modified peptide that is required for aerial growth; and ClpP1, an ATP-dependent protease. The diverse influence of AdpAScprotein on the expression of the analyzed genes presumably results mainly from different affinities of AdpAScprotein to individual promoters.

scholarly journals The zebrafish space cadet gene controls axonal pathfinding of neurons that modulate fast turning movements

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 2131-2142
Author(s):  
Kristin Lorent ◽  
Katherine S. Liu ◽  
Joseph R. Fetcho ◽  
Michael Granato
Keyword(s):  
Neural Circuits ◽  
Motor Behavior ◽  
Neuronal Cell ◽  
Cell Types ◽  
Small Population ◽  
Axonal Pathfinding ◽  
Retinal Ganglion ◽  
Small Set ◽  
On Line ◽  
Axonal Defects

All vertebrates depend on neural circuits to produce propulsive movements; however, the contribution of individual neural cell types to control such movements are not well understood. We report that zebrafish space cadet mutant larvae fail to initiate fast turning movements properly, and we show that this motor phenotype correlates with axonal defects in a small population of commissural hindbrain neurons, which we identify as spiral fiber neurons. Moreover, we demonstrate that severing spiral fiber axons produces space cadet-like locomotor defects, thereby providing compelling evidence that the space cadet gene plays an essential role in integrating these neurons into the circuitry that modulates fast turning movements. Finally, we show that axonal defects are restricted to a small set of commissural trajectories, including retinal ganglion cell axons and spiral fiber axons, and that the space cadet gene functions in axonal pathfinding. Together, our results provide a rare example in vertebrates of an individual neuronal cell type that contributes to the expression of a defined motor behavior. Movies available on-line

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