scholarly journals Synaptic Hyaluronan Synthesis and CD44-Mediated Signaling Coordinate Neural Circuit Development

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2574
Author(s):  
Emily S. Wilson ◽  
Karen Litwa
Keyword(s):  
Mouse Brain ◽  
Synapse Formation ◽  
Neural Circuits ◽  
Neural Circuit ◽  
System Development ◽  
Synaptic Cleft ◽  
Nervous System Development ◽  
Inhibitory Synapses ◽  
Perineuronal Nets ◽  
Potential Formation

The hyaluronan-based extracellular matrix is expressed throughout nervous system development and is well-known for the formation of perineuronal nets around inhibitory interneurons. Since perineuronal nets form postnatally, the role of hyaluronan in the initial formation of neural circuits remains unclear. Neural circuits emerge from the coordinated electrochemical signaling of excitatory and inhibitory synapses. Hyaluronan localizes to the synaptic cleft of developing excitatory synapses in both human cortical spheroids and the neonatal mouse brain and is diminished in the adult mouse brain. Given this developmental-specific synaptic localization, we sought to determine the mechanisms that regulate hyaluronan synthesis and signaling during synapse formation. We demonstrate that hyaluronan synthase-2, HAS2, is sufficient to increase hyaluronan levels in developing neural circuits of human cortical spheroids. This increased hyaluronan production reduces excitatory synaptogenesis, promotes inhibitory synaptogenesis, and suppresses action potential formation. The hyaluronan receptor, CD44, promotes hyaluronan retention and suppresses excitatory synaptogenesis through regulation of RhoGTPase signaling. Our results reveal mechanisms of hyaluronan synthesis, retention, and signaling in developing neural circuits, shedding light on how disease-associated hyaluronan alterations can contribute to synaptic defects.

scholarly journals Cell-type specific patterned stimulus-independent neuronal activity in the Drosophila visual system during synapse formation

2018 ◽  
Author(s):  
Orkun Akin ◽  
Bryce T. Bajar ◽  
Mehmet F. Keles ◽  
Mark A. Frye ◽  
S. Lawrence Zipursky
Keyword(s):  
Visual System ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Specific Activity ◽  
System Development ◽  
Nervous System Development ◽  
Adult Brain ◽  
Cell Type ◽  
Cell Type Specific

SummaryStereotyped synaptic connections define the neural circuits of the brain. In vertebrates, stimulus-independent activity contributes to neural circuit formation. It is unknown whether this type of activity is a general feature of nervous system development. Here, we report patterned, stimulus-independent neural activity in the Drosophila visual system during synaptogenesis. Using in vivo calcium, voltage, and glutamate imaging, we found that all neurons participate in this spontaneous activity, which is characterized by brain-wide periodic active and silent phases. Glia are active in a complementary pattern. Each of the 15 examined of the over 100 specific neuron types in the fly visual system exhibited a unique activity signature. The activity of neurons that are synaptic partners in the adult was highly correlated during development. We propose that this cell type-specific activity coordinates the development of the functional circuitry of the adult brain.

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 Differing strategies used by motor neurons and glia to achieve robust development of an adult neuropil in Drosophila

2017 ◽  
Author(s):  
Jonathan Enriquez ◽  
Laura Quintana Rio ◽  
Richard Blazeski ◽  
Carol Mason ◽  
Richard S. Mann
Keyword(s):  
Stem Cells ◽  
Nervous System ◽  
Birth Order ◽  
Motor Neurons ◽  
Neural Circuits ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Factor Code ◽  
Individual Motor

SummaryIn both vertebrates and invertebrates, neurons and glia are generated in a stereotyped order from dedicated progenitors called neural stem cells, but the purpose of invariant lineages is not understood. Here we show that three of the stem cells that produce leg motor neurons in Drosophila also generate a specialized subset of glia, the neuropil glia, which wrap and send processes into the neuropil where motor neuron dendrites arborize. The development of the neuropil glia and leg motor neurons is highly coordinated. However, although individual motor neurons have a stereotyped birth order and transcription factor code, both the number and individual morphologies of the glia born from these lineages are highly plastic, even though the final structure they contribute to is highly stereotyped. We suggest that the shared lineages of these two cell types facilitates the assembly of complex neural circuits, and that the two different birth order strategies – hardwired for motor neurons and flexible for glia – are important for robust nervous system development and homeostasis.

scholarly journals The development of early pioneer neurons in the annelid Malacoceros fuliginosus

2020 ◽  
Author(s):  
Suman Kumar ◽  
Sharat Chandra Tumu ◽  
Conrad Helm ◽  
Harald Hausen
Keyword(s):  
Nervous System ◽  
Synapse Formation ◽  
System Development ◽  
Posterior Pole ◽  
Nervous System Development ◽  
Whole Body ◽  
Neural Patterning ◽  
Neuronal Progenitors ◽  
Pioneer Neurons ◽  
Clonal Origin

Abstract Background Nervous system development is an interplay of many processes: the formation of individual neurons, which depends on whole-body and local patterning processes, and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the first steps of nervous system development in the annelid Malacoceros fuliginosus . Results Here, we performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 hours postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d 221 ), which after 7 cleavages starts expressing Neurogenin , Achaete-Scute and NeuroD . Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. The specification of the relevant neurons starts very early and we suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.

scholarly journals Knockdown of butyrylcholinesterase but not inhibition by chlorpyrifos alters early differentiation mechanisms in human neural stem cells

2018 ◽  
Author(s):  
Angela K. Tiethof ◽  
Jason R. Richardson ◽  
Ronald P. Hart
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Synapse Formation ◽  
System Development ◽  
Nervous System Development ◽  
Differentiation Markers ◽  
Human Neural Stem Cells ◽  
Early Neurogenesis ◽  
Induced Pluripotent

AbstractButyrylcholinesterase (BChE) is the evolutionary counterpart to acetylcholinesterase (AChE). Both are expressed early in nervous system development prior to cholinergic synapse formation. The organophosphate pesticide chlorpyrifos (CPF) primarily exerts toxicity through inhibition of AChE, which results in excess cholinergic stimulation at the synapse. We hypothesized that inhibition of AChE and BChE by CPF may impair early neurogenesis in neural stem cells (NSCs). To model neurodevelopment in vitro, we used human NSCs derived from induced pluripotent stem cells (iPSCs) with a focus on initial differentiation mechanisms. Over six days of NSC differentiation, BChE activity and mRNA expression significantly increased, while AChE activity and expression remained unchanged. CPF treatment (10 μM) caused 82% and 92% inhibition of AChE and BChE, respectively. CPF exposure had no effect on cell viability or the expression of differentiation markers HES5, DCX or MAP2. However, shRNA-knockdown of BChE expression resulted in decreased or delayed expression of transcription factors HES5 and HES3. BChE may have a role in the differentiation of NSCs independent of, or in addition to, its enzymatic activity.

scholarly journals Knockdown of Butyrylcholinesterase but Not Inhibition by Chlorpyrifos Alters Early Differentiation Mechanisms in Human Neural Stem Cells

Toxics ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 52 ◽  
Author(s):  
Angela Tiethof ◽  
Jason Richardson ◽  
Ronald Hart
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Synapse Formation ◽  
System Development ◽  
Nervous System Development ◽  
Differentiation Markers ◽  
Human Neural Stem Cells ◽  
Early Neurogenesis ◽  
Induced Pluripotent

Butyrylcholinesterase (BChE) is the evolutionary counterpart to acetylcholinesterase (AChE). Both are expressed early in nervous system development prior to cholinergic synapse formation. The organophosphate pesticide chlorpyrifos (CPF) primarily exerts toxicity through the inhibition of AChE, which results in excess cholinergic stimulation at the synapse. We hypothesized that the inhibition of AChE and BChE by CPF may impair early neurogenesis in neural stem cells (NSCs). To model neurodevelopment in vitro, we used human NSCs derived from induced pluripotent stem cells (iPSCs) with a focus on the initial differentiation mechanisms. Over the six days of NSC differentiation, the BChE activity and mRNA expression significantly increased, while the AChE activity and expression remained unchanged. The CPF treatment (10 μM) caused 82% and 92% inhibition of AChE and BChE, respectively. The CPF exposure had no effect on the cell viability or the expression of the differentiation markers HES5, DCX, or MAP2. However, the shRNA-knockdown of the BChE expression resulted in the decreased or delayed expression of the transcription factors HES5 and HES3. BChE may have a role in the differentiation of NSCs independent of, or in addition to, its enzymatic activity.

scholarly journals Connect-seq to superimpose molecular on anatomical neural circuit maps

2020 ◽  
Vol 117 (8) ◽  
pp. 4375-4384 ◽  
Author(s):  
Naresh K. Hanchate ◽  
Eun Jeong Lee ◽  
Andria Ellis ◽  
Kunio Kondoh ◽  
Donghui Kuang ◽  
...  
Keyword(s):  
Single Cell ◽  
Mouse Brain ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Physiological Responses ◽  
Signaling Molecules ◽  
Hypothalamic Neurons ◽  
Vast Array ◽  
Molecular Map

The mouse brain contains about 75 million neurons interconnected in a vast array of neural circuits. The identities and functions of individual neuronal components of most circuits are undefined. Here we describe a method, termed “Connect-seq,” which combines retrograde viral tracing and single-cell transcriptomics to uncover the molecular identities of upstream neurons in a specific circuit and the signaling molecules they use to communicate. Connect-seq can generate a molecular map that can be superimposed on a neuroanatomical map to permit molecular and genetic interrogation of how the neuronal components of a circuit control its function. Application of this method to hypothalamic neurons controlling physiological responses to fear and stress reveals subsets of upstream neurons that express diverse constellations of signaling molecules and can be distinguished by their anatomical locations.

scholarly journals The development of early pioneer neurons in the annelid Malacoceros fuliginosus

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Suman Kumar ◽  
Sharat Chandra Tumu ◽  
Conrad Helm ◽  
Harald Hausen
Keyword(s):  
Nervous System ◽  
Synapse Formation ◽  
System Development ◽  
Posterior Pole ◽  
Nervous System Development ◽  
Whole Body ◽  
Neural Patterning ◽  
Neuronal Progenitors ◽  
Pioneer Neurons ◽  
Clonal Origin

Abstract Background Nervous system development is an interplay of many processes: the formation of individual neurons, which depends on whole-body and local patterning processes, and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the first steps of nervous system development in the annelid Malacoceros fuliginosus. Results We performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 h postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d221), which after 7 cleavages starts expressing Neurogenin, Acheate-Scute and NeuroD. Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. We suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.

scholarly journals Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ming Zhang ◽  
Jian Wang ◽  
Kaixiang Zhang ◽  
Guozhen Lu ◽  
Yuming Liu ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Intracellular Signaling ◽  
System Development ◽  
Nervous System Development ◽  
Oligodendrocyte Progenitor Cells ◽  
Calcium Activity ◽  
Dna Hydroxymethylation ◽  
Tet Proteins ◽  
A Genome

AbstractTen-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of Tet1 results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking Tet1 in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport. Tet1-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene, Itpr2, impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.

scholarly journals Drosophila ClC-a is required in glia of the stem cell niche for proper neurogenic proliferation and wiring of neural circuits

2018 ◽  
Author(s):  
Haritz Plazaola-Sasieta ◽  
Qi Zhu ◽  
Héctor Gaitán-Peñas ◽  
Martín Rios ◽  
Raúl Estévez ◽  
...  
Keyword(s):  
Stem Cell ◽  
Glial Cells ◽  
Stem Cell Niche ◽  
Neural Circuits ◽  
System Development ◽  
Nervous System Development ◽  
Loss Of Function ◽  
Cell Niche ◽  
Neuroblast Proliferation ◽  
Photoreceptor Axon Guidance

ABSTRACTGlial cells form part of the neural stem cell niche and express a wide variety of ion channels; however, the contribution of these channels to nervous system development is poorly understood. We explored the function of the Drosophila ClC-a chloride channel, since its mammalian ortholog CLCN2 is expressed in glial cells, and defective channel function results in leukodystrophies, which in humans are accompanied by cognitive impairment. We found that ClC-a was expressed in the niche in cortex glia, which are closely associated with neurogenic tissues. Characterization of loss-of-function ClC-a mutants revealed that these animals had smaller brains and widespread wiring defects. We showed that ClC-a is required in cortex glia for neuroepithelia and neuroblast proliferation and identified defects in a neuroblast lineage that generates guidepost glial cells essential for photoreceptor axon guidance. We propose that glia-mediated ionic homeostasis could non-autonomously affect neurogenesis, and consequently, the correct assembly of neural circuits.

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