scholarly journals Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity

2020 ◽  
Author(s):  
Daniel Z. Doyle ◽  
Mandy M. Lam ◽  
Adel Qalieh ◽  
Yaman Qalieh ◽  
Alice Sorel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Axon Guidance ◽  
Neural Circuits ◽  
Cortical Plate ◽  
Chromatin Remodeler ◽  
Cortical Connectivity ◽  
Molecular Identity ◽  
Subplate Neurons ◽  
Cell Type Specific ◽  
And Function

AbstractSubplate neurons indispensably orchestrate the developmental assembly of cortical neural circuits. Here, by cell type-specific dissection of Arid1a function, we uncover an unexpectedly selective role for this ubiquitous chromatin remodeler in subplate neuron molecular identity and circuit wiring function. We find that pan-cortical deletion of Arid1a, but not sparse deletion, leads to mistargeting of callosal and thalamocortical connectivities reminiscent of subplate ablation. These miswiring phenotypes are concomitant with disrupted subplate neuron organization, morphogenesis, axons, and extracellular matrix. Mechanistically, Arid1a is required to establish the transcriptional identity of subplate neurons. Remarkably, cortical plate deletion of Arid1a, which spares subplate neurons, restores subplate axons and extracellular matrix, and is sufficient to extensively correct callosal and thalamocortical axon misrouting, revealing an axon guidance function of Arid1a centered on the subplate. Thus, Arid1a regulates the molecular identity and function of subplate neurons, and thereby non-cell autonomously mediates the formation of cortical connectivity during development.

scholarly journals Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity

2021 ◽  
Vol 118 (21) ◽  
pp. e2100686118
Author(s):  
Daniel Z. Doyle ◽  
Mandy M. Lam ◽  
Adel Qalieh ◽  
Yaman Qalieh ◽  
Alice Sorel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Corpus Callosum ◽  
Neural Circuit ◽  
Cortical Plate ◽  
Loss Of Function ◽  
Chromatin Remodeler ◽  
Agenesis Of Corpus Callosum ◽  
Axon Targeting ◽  
Subplate Neurons ◽  
Multiple Characteristics

Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation (“handshake”), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.

scholarly journals Roles for the adhension molecule Contactin2 in the development and function of neural circuits in zebrafish

2018 ◽  
Author(s):  
◽  
Suman Gurung
Keyword(s):  
Axon Guidance ◽  
Neuronal Migration ◽  
Neural Circuits ◽  
Genetic Interactions ◽  
Bacterial Toxin ◽  
Neuron Migration ◽  
Cell Ablation ◽  
Cell Substrate ◽  
And Function ◽  
Human Cd59

Neuronal migration and axon guidance are critical developmental processes that are essential for establishing functional neural circuits underlying complex cognitive and motor functions. Precise neuronal migration and axon guidance are dependent upon cell-cell and cell-substrate interactions, which are mediated by several membrane-associated molecules. The relatively concise segmental organization of the hindbrain and the simple scaffold of axon tracts in the zebrafish brain provides an ideal model to study how different molecules collaborate to guide migrating neurons and growing axons to their final location. In this thesis, I examine the roles of membrane molecules during neuron migration and axon guidance in zebrafish. In Chapter 3, I show the generation of Contactin2 (Cntn2) null mutant using CRISPR/Cas9 and characterize cntn2 mutant. I demonstrate a role for cntn2 in facial branchiomotor (FBM) neuron migration and fasciculation of medial longitudinal fascicle (MLF) axons. In addition, using touch-evoked escape response and swimming assays, I show sensorimotor deficits in cntn2 mutants. Collectively, these data demonstrate distinct developmental roles for zebrafish cntn2 in neuronal migration and axon fasciculation, and in the function of sensorimotor circuits. In Chapter 4, I examine pairwise genetic interactions between several PCP and non-PCP genes for FBM neuron migration. I show that vangl2 is rather unique in exhibiting genetic interactions with several PCP and non-PCP genes. These data suggest that vangl2 might be playing a central role in regulating the function of many PCP and non-PCP genes for FBM neuron migration. In Chapter 6, I describe a novel genetic approach which utilizes the human CD59 receptor (hCD59) and the bacterial toxin intermedilysin (ILY) for rapid cell ablation in zebrafish.

Enhanced Structure and Function of Stem Cell-Derived Beta-Like Cells Cultured on Extracellular Matrix

2020 ◽  
Author(s):  
Reena Singh ◽  
Richard Tan ◽  
Clara Tran ◽  
Thomas Loudovaris ◽  
Helen E. Thomas ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Structure And Function ◽  
And Function ◽  
Cells Cultured

scholarly journals From Exosome Glycobiology to Exosome Glycotechnology, the Role of Natural Occurring Polysaccharides

2021 ◽  
Vol 2 (2) ◽  
pp. 311-338
Author(s):  
Giulia Della Rosa ◽  
Clarissa Ruggeri ◽  
Alessandra Aloisi
Keyword(s):  
State Of The Art ◽  
Cell Communication ◽  
Pathological Conditions ◽  
New Findings ◽  
Cell Type Specific ◽  
New Perspective ◽  
And Function ◽  
And Personalized Medicine ◽  
Innate Ability

Exosomes (EXOs) are nano-sized informative shuttles acting as endogenous mediators of cell-to-cell communication. Their innate ability to target specific cells and deliver functional cargo is recently claimed as a promising theranostic strategy. The glycan profile, actively involved in the EXO biogenesis, release, sorting and function, is highly cell type-specific and frequently altered in pathological conditions. Therefore, the modulation of EXO glyco-composition has recently been considered an attractive tool in the design of novel therapeutics. In addition to the available approaches involving conventional glyco-engineering, soft technology is becoming more and more attractive for better exploiting EXO glycan tasks and optimizing EXO delivery platforms. This review, first, explores the main functions of EXO glycans and associates the potential implications of the reported new findings across the nanomedicine applications. The state-of-the-art of the last decade concerning the role of natural polysaccharides—as targeting molecules and in 3D soft structure manufacture matrices—is then analysed and highlighted, as an advancing EXO biofunction toolkit. The promising results, integrating the biopolymers area to the EXO-based bio-nanofabrication and bio-nanotechnology field, lay the foundation for further investigation and offer a new perspective in drug delivery and personalized medicine progress.

scholarly journals Function of Circular RNAs in Fish and Their Potential Application as Biomarkers

2021 ◽  
Vol 22 (13) ◽  
pp. 7119
Author(s):  
Golam Rbbani ◽  
Artem Nedoluzhko ◽  
Jorge Galindo-Villegas ◽  
Jorge M. O. Fernandes
Keyword(s):  
Growth Regulation ◽  
Functional Characterization ◽  
Circular Rnas ◽  
Farmed Fish ◽  
Developmentally Regulated ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Taxonomic Groups ◽  
And Function

Circular RNAs (circRNAs) are an emerging class of regulatory RNAs with a covalently closed-loop structure formed during pre-mRNA splicing. Recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of novel approaches to their identification and functional characterization. CircRNAs are stable, developmentally regulated, and show tissue- and cell-type-specific expression across different taxonomic groups. They play a crucial role in regulating various biological processes at post-transcriptional and translational levels. However, the involvement of circRNAs in fish immunity has only recently been recognized. There is also broad evidence in mammals that the timely expression of circRNAs in muscle plays an essential role in growth regulation but our understanding of their expression and function in teleosts is still very limited. Here, we discuss the available knowledge about circRNAs and their role in growth and immunity in vertebrates from a comparative perspective, with emphasis on cultured teleost fish. We expect that the interest in teleost circRNAs will increase substantially soon, and we propose that they may be used as biomarkers for selective breeding of farmed fish, thus contributing to the sustainability of the aquaculture sector.

scholarly journals Neurons interact with the microbiome: an evolutionary-informed perspective

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Giez ◽  
Alexander Klimovich ◽  
Thomas C. G. Bosch
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Comprehensive Understanding ◽  
Strategic Model ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function

Abstract Animals have evolved within the framework of microbes and are constantly exposed to diverse microbiota. Microbes colonize most, if not all, animal epithelia and influence the activity of many organs, including the nervous system. Therefore, any consideration on nervous system development and function in the absence of the recognition of microbes will be incomplete. Here, we review the current knowledge on the nervous systems of Hydra and its role in the host–microbiome communication. We show that recent advances in molecular and imaging methods are allowing a comprehensive understanding of the capacity of such a seemingly simple nervous system in the context of the metaorganism. We propose that the development, function and evolution of neural circuits must be considered in the context of host–microbe interactions and present Hydra as a strategic model system with great basic and translational relevance for neuroscience.

scholarly journals Extracellular Matrix Regulates UNC-6 (Netrin) Axon Guidance by Controlling the Direction of Intracellular UNC-40 (DCC) Outgrowth Activity

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e97258 ◽  
Author(s):  
Yong Yang ◽  
Won Suk Lee ◽  
Xia Tang ◽  
William G. Wadsworth
Keyword(s):  
Extracellular Matrix ◽  
Axon Guidance

scholarly journals Proteolytic Events of Wound-Healing — Coordinated Interactions Among Matrix Metalloproteinases (MMPs), Integrins, and Extracellular Matrix Molecules

2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Matrix Metalloproteinases ◽  
Wound Repair ◽  
Enzyme Activation ◽  
Processing Enzymes ◽  
The Matrix ◽  
Signaling Receptors ◽  
State Of Rest ◽  
And Function

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.

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