scholarly journals Correct Laminar Positioning in the Neocortex Influences Proper Dendritic and Synaptic Development

2018 ◽  
Vol 28 (8) ◽  
pp. 2976-2990 ◽  
Author(s):  
Fanny Sandrine Martineau ◽  
Surajit Sahu ◽  
Vanessa Plantier ◽  
Emmanuelle Buhler ◽  
Fabienne Schaller ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Synapse Formation ◽  
Functional Organization ◽  
Functional Integration ◽  
Proper Function ◽  
Cortical Circuits ◽  
Gabaergic Synapses ◽  
Dendrite Morphogenesis

Abstract The neocortex is a 6-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down doublecortin (Dcx), a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines, and functional glutamatergic and GABAergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.

scholarly journals Correct laminar positioning in the neocortex influences proper dendritic and synaptic development

2017 ◽  
Author(s):  
Fanny Sandrine Martineau ◽  
Surajit Sahu ◽  
Vanessa Plantier ◽  
Emmanuelle Buhler ◽  
Fabienne Schaller ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Synapse Formation ◽  
Functional Organization ◽  
Functional Integration ◽  
Proper Function ◽  
Cortical Circuits ◽  
Glutamatergic Synapses ◽  
Dendrite Morphogenesis

AbstractThe neocortex is a six-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down Dcx, a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines and functional glutamatergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.

scholarly journals Neurotrophic Effect of Fish-Lecithin Based Nanoliposomes on Cortical Neurons

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 406 ◽  
Author(s):  
Catherine Malaplate ◽  
Aurelia Poerio ◽  
Marion Huguet ◽  
Claire Soligot ◽  
Elodie Passeri ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Synapse Formation ◽  
Fatty Acid Content ◽  
Primary Cultures ◽  
Synaptic Membrane ◽  
Neuronal Membranes ◽  
Acid Ratio ◽  
And Function

Lipids play multiple roles in preserving neuronal function and synaptic plasticity, and polyunsaturated fatty acids (PUFAs) have been of particular interest in optimizing synaptic membrane organization and function. We developed a green-based methodology to prepare nanoliposomes (NL) from lecithin that was extracted from fish head by-products. These NL range between 100–120 nm in diameter, with an n-3/n-6 fatty acid ratio of 8.88. The high content of n-3 PUFA (46.3% of total fatty acid content) and docosahexanoic acid (26%) in these NL represented a means for enrichment of neuronal membranes that are potentially beneficial for neuronal growth and synaptogenesis. To test this, the primary cultures of rat embryo cortical neurons were incubated with NL on day 3 post-culture for 24 h, followed by immunoblots or immunofluorescence to evaluate the NL effects on synaptogenesis, axonal growth, and dendrite formation. The results revealed that NL-treated cells displayed a level of neurite outgrowth and arborization on day 4 that was similar to those of untreated cells on day 5 and 6, suggesting accelerated synapse formation and neuronal development in the presence of NL. We propose that fish-derived NL, by virtue of their n-3 PUFA profile and neurotrophic effects, represent a new innovative bioactive vector for developing preventive or curative treatments for neurodegenerative diseases.

Pre- and post-synaptic mechanisms regulating the clustering of type A γ-aminobutyric acid receptors (GABAA receptors)

2003 ◽  
Vol 31 (4) ◽  
pp. 889-892 ◽  
Author(s):  
J.-M. Fritschy ◽  
C. Schweizer ◽  
I. Brünig ◽  
B. Lüscher
Keyword(s):  
Neuronal Activity ◽  
Protein Complex ◽  
Gabaa Receptors ◽  
Synapse Formation ◽  
Type A ◽  
Aminobutyric Acid ◽  
Proper Function ◽  
Gabaergic Synapses ◽  
Synaptic Mechanisms

Postsynaptic clustering of GABAA (type A γ-aminobutyric acid) receptors is essential to ensure proper function of GABAergic synapses. This process is initiated during synapse formation and is maintained throughout life. The tubulin-associated protein gephyrin is required for clustering of GABAA receptors, but its specific role in this process is not understood. A second protein associated selectively with GABAA receptors at postsynaptic sites is dystrophin. It is present in a subset of GABAergic synapses along with several partners, forming the dystrophin-associated protein complex. In this review, we discuss recent advances in the role of neuronal activity and trans-synaptic signaling for the clustering of gephyrin and dystrophin during synaptogenesis and on the role of these proteins for plasticity and maintenance of mature synapses.

scholarly journals Septin 14 Is Involved in Cortical Neuronal Migration via Interaction with Septin 4

2010 ◽  
Vol 21 (8) ◽  
pp. 1324-1334 ◽  
Author(s):  
Tomoyasu Shinoda ◽  
Hidenori Ito ◽  
Kaori Sudo ◽  
Ikuko Iwamoto ◽  
Rika Morishita ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Migration ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Cell Cycle Control ◽  
Coiled Coil ◽  
Cortical Plate ◽  
Process Formation ◽  
Biochemical Analyses

Septins are a family of conserved guanosine triphosphate/guanosine diphosphate-binding proteins implicated in a variety of cellular functions such as cell cycle control and cytokinesis. Although several members of septin family, including Septin 14 (Sept14), are abundantly expressed in nervous tissues, little is known about their physiological functions, especially in neuronal development. Here, we report that Sept14 is strongly expressed in the cortical plate of developing cerebral cortex. Knockdown experiments by using the method of in utero electroporation showed that reduction of Sept14 caused inhibition of cortical neuronal migration. Whereas cDNA encoding RNA interference-resistant Sept14 rescued the migration defect, the C-terminal deletion mutant of Sept14 did not. Biochemical analyses revealed that C-terminal coiled-coil region of Sept14 interacts with Septin 4 (Sept4). Knockdown experiments showed that Sept4 is also involved in cortical neuronal migration in vivo. In addition, knockdown of Sept14 or Sept4 inhibited leading process formation in migrating cortical neurons. These results suggest that Sept14 is involved in neuronal migration in cerebral cortex via interaction with Sept4.

scholarly journals Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission

2019 ◽  
Vol 5 (9) ◽  
pp. eaax2166 ◽  
Author(s):  
Hui Guo ◽  
Ying Li ◽  
Lu Shen ◽  
Tianyun Wang ◽  
Xiangbin Jia ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Cortical Neurons ◽  
Posttranscriptional Regulation ◽  
Neuronal Development ◽  
Rna Binding ◽  
Synapse Formation ◽  
Rna Binding Proteins ◽  
Motor Delay ◽  
Primary Mouse ◽  
Significant Burden

RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity–related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

Central Nervous System Embryogenesis and Its Failures

2002 ◽  
Vol 5 (5) ◽  
pp. 425-447 ◽  
Author(s):  
Felicitas L. Lacbawan ◽  
Maximilian Muenke
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuronal Migration ◽  
Intracellular Signaling ◽  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Proper Function ◽  
Stages Of Development ◽  
Regulatory Processes

The well-orchestrated development of the central nervous system (CNS) requires highly integrated regulatory processes to ensure its precise spatial organization that provides the foundation for proper function. As emphasized in this review, the type, timing, and location of regulatory molecules influence the different stages of development from neuronal induction, regional specification, neuronal specification, and neuronal migration to axonal growth and guidance, neuronal survival, and synapse formation. The known molecular mechanisms are summarized from studies of invertebrates and lower vertebrates, in which we have learned more about the different ligands, receptors, transcription factors, and the intracellular signaling pathways that play specific roles in the different stages of development. Despite known molecular mechanisms of some disturbances, most of the clinical entities that arise from failures of CNS embryogenesis remain unexplained. As more novel genes and their functions are discovered, existing mechanisms will be refined and tenable explanations will be made. With these limitations, two specific clinical entities that have been relatively well studied, holoprosen-cephaly and neuronal migration defects, are discussed in more detail to illustrate the complexity of regulatory mechanisms that govern well-defined stages of CNS development.

scholarly journals The unbalanced reorganization of weaker functional connections induces the altered brain network topology in schizophrenia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rossana Mastrandrea ◽  
Fabrizio Piras ◽  
Andrea Gabrielli ◽  
Nerisa Banaj ◽  
Guido Caldarelli ◽  
...  
Keyword(s):  
Resting State ◽  
Functional Organization ◽  
Functional Integration ◽  
Brain Network ◽  
Modular Organization ◽  
Node Degree ◽  
Imaging Data ◽  
Brain Disorder ◽  
Functional Connections ◽  
The Brain

AbstractNetwork neuroscience shed some light on the functional and structural modifications occurring to the brain associated with the phenomenology of schizophrenia. In particular, resting-state functional networks have helped our understanding of the illness by highlighting the global and local alterations within the cerebral organization. We investigated the robustness of the brain functional architecture in 44 medicated schizophrenic patients and 40 healthy comparators through an advanced network analysis of resting-state functional magnetic resonance imaging data. The networks in patients showed more resistance to disconnection than in healthy controls, with an evident discrepancy between the two groups in the node degree distribution computed along a percolation process. Despite a substantial similarity of the basal functional organization between the two groups, the expected hierarchy of healthy brains' modular organization is crumbled in schizophrenia, showing a peculiar arrangement of the functional connections, characterized by several topologically equivalent backbones. Thus, the manifold nature of the functional organization’s basal scheme, together with its altered hierarchical modularity, may be crucial in the pathogenesis of schizophrenia. This result fits the disconnection hypothesis that describes schizophrenia as a brain disorder characterized by an abnormal functional integration among brain regions.

scholarly journals Multiple Alu exonization in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge

2020 ◽  
Author(s):  
Aniket Bhattacharya ◽  
Vineet Jha ◽  
Khushboo Singhal ◽  
Mahar Fatima ◽  
Dayanidhi Singh ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cortical Neurons ◽  
Regulatory Networks ◽  
Large Scale ◽  
Neuronal Development ◽  
Random Sets ◽  
Rna Seq ◽  
Orphan Gene ◽  
Mirna Sponge ◽  
Human Neurons

Abstract Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Our study highlights how exonized Alus could nucleate large-scale mRNA-miRNA interactions. Using a functional genomics approach, we characterize a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that has exonization of 23 Alus in its 3’UTR. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9 kb 3’UTR) and widely expressed. Using publically available datasets, we demonstrate its expression in higher primates and presence in single nucleus RNA-seq of 15928 human cortical neurons. miRanda predicts ∼4700 miRNA recognition elements (MREs) for ∼1000 miRNAs, primarily originated within these 3’UTR-Alus. CYP20A1_Alu-LT could be a potential multi-miRNA sponge as it harbors ≥10 MREs for 140 miRNAs and has cytosolic localization. We further tested whether expression of CYP20A1_Alu-LT correlates with mRNAs harboring similar MRE targets. RNA-seq with conjoint miRNA-seq analysis was done in primary human neurons where we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. 380 genes were positively correlated with its expression (significantly downregulated in heat shock and upregulated in Tat) and they harbored MREs for nine expressed miRNAs which were also enriched in CYP20A1_Alu-LT. MREs were significantly enriched in these 380 genes compared to random sets of differentially expressed genes (p = 8.134e-12). Gene ontology suggested involvement of these genes in neuronal development and hemostasis pathways thus proposing a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.

Block of synapse formation between cerebral cortical neurons by a protein kinase inhibitor

1992 ◽  
Vol 135 (2) ◽  
pp. 255-258 ◽  
Author(s):  
Yoichiro Kuroda ◽  
Masumi Ichikawa ◽  
Kazuyo Muramoto ◽  
Kazuo Kobayashi ◽  
Yuzuru Matsuda ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cortical Neurons ◽  
Synapse Formation ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Cerebral Cortical Neurons

scholarly journals KBP interacts with SCG10, linking Goldberg–Shprintzen syndrome to microtubule dynamics and neuronal differentiation

2010 ◽  
Vol 19 (18) ◽  
pp. 3642-3651 ◽  
Author(s):  
Maria M. Alves ◽  
Grzegorz Burzynski ◽  
Jean-Marie Delalande ◽  
Jan Osinga ◽  
Annemieke van der Goot ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Neuronal Differentiation ◽  
Cortical Neurons ◽  
Neuronal Development ◽  
Direct Interaction ◽  
Clinical Disorder ◽  
Neurite Development

Abstract Goldberg–Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in nerve growth factor-induced differentiation and neurite outgrowth, suggesting that KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo . To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.

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