scholarly journals Current Advances in Comprehending Dynamics of Regenerating Axons and Axon–Glia Interactions after Peripheral Nerve Injury in Zebrafish

2021 ◽  
Vol 22 (5) ◽  
pp. 2484
Author(s):  
David Gonzalez ◽  
Miguel L. Allende
Keyword(s):  
Nervous System ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Time Lapse ◽  
Cell Types ◽  
Regenerative Process ◽  
Time Lapse Microscopy ◽  
Different Cell Types

Following an injury, axons of both the central nervous system (CNS) and peripheral nervous system (PNS) degenerate through a coordinated and genetically conserved mechanism known as Wallerian degeneration (WD). Unlike central axons, severed peripheral axons have a higher capacity to regenerate and reinnervate their original targets, mainly because of the favorable environment that they inhabit and the presence of different cell types. Even though many aspects of regeneration in peripheral nerves have been studied, there is still a lack of understanding regarding the dynamics of axonal degeneration and regeneration, mostly due to the inherent limitations of most animal models. In this scenario, the use of zebrafish (Danio rerio) larvae combined with time-lapse microscopy currently offers a unique experimental opportunity to monitor the dynamics of the regenerative process in the PNS in vivo. This review summarizes the current knowledge and advances made in understanding the dynamics of the regenerative process of PNS axons. By using different tools available in zebrafish such as electroablation of the posterior lateral line nerve (pLLn), and laser-mediated transection of motor and sensory axons followed by time-lapse microscopy, researchers are beginning to unravel the complexity of the spatiotemporal interactions among different cell types during the regenerative process. Thus, understanding the cellular and molecular mechanisms underlying the degeneration and regeneration of peripheral nerves will open new avenues in the treatment of acute nerve trauma or chronic conditions such as neurodegenerative diseases.

scholarly journals Filopodyan: An open-source pipeline for the analysis of filopodia

2017 ◽  
Vol 216 (10) ◽  
pp. 3405-3422 ◽  
Author(s):  
Vasja Urbančič ◽  
Richard Butler ◽  
Benjamin Richier ◽  
Manuel Peter ◽  
Julia Mason ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Dynamic Properties ◽  
Cell Types ◽  
Molecular Heterogeneity ◽  
Interactive Editing ◽  
Motile Cells ◽  
Different Cell Types ◽  
Neuronal Growth Cones

Filopodia have important sensory and mechanical roles in motile cells. The recruitment of actin regulators, such as ENA/VASP proteins, to sites of protrusion underlies diverse molecular mechanisms of filopodia formation and extension. We developed Filopodyan (filopodia dynamics analysis) in Fiji and R to measure fluorescence in filopodia and at their tips and bases concurrently with their morphological and dynamic properties. Filopodyan supports high-throughput phenotype characterization as well as detailed interactive editing of filopodia reconstructions through an intuitive graphical user interface. Our highly customizable pipeline is widely applicable, capable of detecting filopodia in four different cell types in vitro and in vivo. We use Filopodyan to quantify the recruitment of ENA and VASP preceding filopodia formation in neuronal growth cones, and uncover a molecular heterogeneity whereby different filopodia display markedly different responses to changes in the accumulation of ENA and VASP fluorescence in their tips over time.

scholarly journals When fate follows age: unequal centrosomes in asymmetric cell division

2014 ◽  
Vol 369 (1650) ◽  
pp. 20130466 ◽  
Author(s):  
Jose Reina ◽  
Cayetano Gonzalez
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Strong Correlation ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Current Knowledge ◽  
Cell Types ◽  
Functional Implications ◽  
Different Cell Types ◽  
Review Current

A strong correlation between centrosome age and fate has been reported in some stem cells and progenitors that divide asymmetrically. In some cases, such stereotyped centrosome behaviour is essential to endow stemness to only one of the two daughters, whereas in other cases causality is still uncertain. Here, we present the different cell types in which correlated centrosome age and fate has been documented, review current knowledge on the underlying molecular mechanisms and discuss possible functional implications of this process.

scholarly journals Deubiquitinase MYSM1 in the Hematopoietic System and beyond: A Current Review

2020 ◽  
Vol 21 (8) ◽  
pp. 3007 ◽  
Author(s):  
Amanda Fiore ◽  
Yue Liang ◽  
Yun Hsiao Lin ◽  
Jacky Tung ◽  
HanChen Wang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Current Knowledge ◽  
Cell Types ◽  
Histone H2a ◽  
Hematopoietic Stem ◽  
Developmental Abnormalities ◽  
Cellular Processes ◽  
Different Cell Types

MYSM1 has emerged as an important regulator of hematopoietic stem cell function, blood cell production, immune response, and other aspects of mammalian physiology. It is a metalloprotease family protein with deubiquitinase catalytic activity, as well as SANT and SWIRM domains. MYSM1 normally localizes to the nucleus, where it can interact with chromatin and regulate gene expression, through deubiquitination of histone H2A and non-catalytic contacts with other transcriptional regulators. A cytosolic form of MYSM1 protein was also recently described and demonstrated to regulate signal transduction pathways of innate immunity, by promoting the deubiquitination of TRAF3, TRAF6, and RIP2. In this work we review the current knowledge on the molecular mechanisms of action of MYSM1 protein in transcriptional regulation, signal transduction, and potentially other cellular processes. The functions of MYSM1 in different cell types and aspects of mammalian physiology are also reviewed, highlighting the key checkpoints in hematopoiesis, immunity, and beyond regulated by MYSM1. Importantly, mutations in MYSM1 in human were recently linked to a rare hereditary disorder characterized by leukopenia, anemia, and other hematopoietic and developmental abnormalities. Our growing knowledge of MYSM1 functions and mechanisms of actions sheds important insights into its role in mammalian physiology and the etiology of the MYSM1-deficiency disorder in human.

Neuropilins: structure, function and role in disease

2008 ◽  
Vol 411 (2) ◽  
pp. 211-226 ◽  
Author(s):  
Caroline Pellet-Many ◽  
Paul Frankel ◽  
Haiyan Jia ◽  
Ian Zachary
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Axonal Guidance ◽  
Vascular Endothelial ◽  
Cardiovascular Development ◽  
Functional Responses ◽  
Tumour Cell Lines ◽  
Endothelial Growth Factor ◽  
Different Cell Types

NRPs (neuropilins) are co-receptors for class 3 semaphorins, polypeptides with key roles in axonal guidance, and for members of the VEGF (vascular endothelial growth factor) family of angiogenic cytokines. They lack a defined signalling role, but are thought to mediate functional responses as a result of complex formation with other receptors, such as plexins in the case of semaphorins and VEGF receptors (e.g. VEGFR2). Mutant mouse studies show that NRP1 is essential for neuronal and cardiovascular development, whereas NRP2 has a more restricted role in neuronal patterning and lymphangiogenesis, but recent findings indicate that NRPs may have additional biological roles in other physiological and disease-related settings. In particular, NRPs are highly expressed in diverse tumour cell lines and human neoplasms and have been implicated in tumour growth and vascularization in vivo. However, despite the wealth of information regarding the probable biological roles of these molecules, many aspects of the regulation of cellular function via NRPs remain uncertain, and little is known concerning the molecular mechanisms through which NRPs mediate the functions of their various ligands in different cell types.

scholarly journals Filopodyan: An Open-Source Pipeline For The Analysis Of Filopodia

2017 ◽  
Author(s):  
Vasja Urbančič ◽  
Richard Butler ◽  
Benjamin Richier ◽  
Manuel Peter ◽  
Julia Mason ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Dynamic Properties ◽  
Cell Types ◽  
Molecular Heterogeneity ◽  
Interactive Editing ◽  
Motile Cells ◽  
Different Cell Types ◽  
Neuronal Growth Cones

Filopodia have important sensory and mechanical roles in motile cells. The recruitment of actin regulators, such as ENA/VASP proteins, to sites of protrusion underlies diverse molecular mechanisms of filopodia formation and extension. We developed Filopodyan ( filopo dia dy namics an alysis) in Fiji and R to measure fluorescence in filopodia and at their tips and bases concurrently with their morphological and dynamic properties. Filopodyan supports high-throughput phenotype characterization as well as detailed interactive editing of filopodia reconstructions through an intuitive graphical user interface. Our highly customizable pipeline is widely applicable, capable of detecting filopodia in four different cell types in vitro and in vivo. We use Filopodyan to show that recruitment of ENA and VASP precedes filopodia formation in neuronal growth cones, and uncover a molecular heterogeneity whereby different filopodia display markedly different responses to changes in the accumulation of ENA and VASP in their tips over time.

p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton

2000 ◽  
Vol 113 (6) ◽  
pp. 975-983 ◽  
Author(s):  
S. Humbert ◽  
R. Dhavan ◽  
L. Tsai
Keyword(s):  
Nervous System ◽  
Subcellular Localization ◽  
Actin Cytoskeleton ◽  
Sequence Homology ◽  
Cell Types ◽  
Serine Threonine Kinase ◽  
Cytoskeletal Dynamics ◽  
Close Sequence ◽  
Different Cell Types

Cyclin-dependent kinase 5 (cdk5) is a small serine/threonine kinase that displays close sequence homology to the mitotically active cyclin-dependent kinases. Cdk5 has been shown to play an essential role in the development of the nervous system, including neuronal migration and neurite outgrowth. Cdk5 activation requires the presence of a regulatory activator such as p35. cdk5 -/- mice have much more extensive defects in the development of the nervous system than p35 -/- mice, leading to the speculation that other regulatory activators of cdk5 exist. Indeed, p39 is a p35 related protein isolated by sequence homology to p35. We show here that p39 associates with cdk5 in brain lysates, and that this complex is active in phosphorylation of histone H1. By extensive characterization of p39 subcellular localization in different cell types, we demonstrate the presence of p39 in lamellipodial and fillopodial structures of cells and in growth cones of neurons. We show that p39 colocalizes with actin, and cofractionates with the detergent insoluble cytoskeleton from brain. Further, p39 coimmunoprecipitates with actin in brain lysates. Finally, disruption of the actin cytoskeleton alters p39 subcellular localization as well as kinase activity of the p39/cdk5 complex. Therefore, our results reveal the existence of the p39/cdk5 complex in vivo and suggest that it might play a role in regulating actin cytoskeletal dynamics in cells.

scholarly journals Zebrafish cardiac regeneration—looking beyond cardiomyocytes to a complex microenvironment

2020 ◽  
Author(s):  
Rebecca Ryan ◽  
Bethany R. Moyse ◽  
Rebecca J. Richardson
Keyword(s):  
Cardiac Injury ◽  
Cell Communication ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Regenerative Process ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Underlying Mechanisms ◽  
Different Cell Types

Abstract The study of heart repair post-myocardial infarction has historically focused on the importance of cardiomyocyte proliferation as the major factor limiting adult mammalian heart regeneration. However, there is mounting evidence that a narrow focus on this one cell type discounts the importance of a complex cascade of cell–cell communication involving a whole host of different cell types. A major difficulty in the study of heart regeneration is the rarity of this process in adult animals, meaning a mammalian template for how this can be achieved is lacking. Here, we review the adult zebrafish as an ideal and unique model in which to study the underlying mechanisms and cell types required to attain complete heart regeneration following cardiac injury. We provide an introduction to the role of the cardiac microenvironment in the complex regenerative process and discuss some of the key advances using this in vivo vertebrate model that have recently increased our understanding of the vital roles of multiple different cell types. Due to the sheer number of exciting studies describing new and unexpected roles for inflammatory cell populations in cardiac regeneration, this review will pay particular attention to these important microenvironment participants.

scholarly journals THE EFFECT OF THYMOSIN β4 ON THE FUNCTIONAL ACTIVITY OF THE IMMUNE AND NERVOUS SYSTEM COMPONENTS

2019 ◽  
Vol 19 (1S) ◽  
pp. 164-166
Author(s):  
V P Ivanova
Keyword(s):  
Nervous System ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Functional Organization ◽  
Intracellular Localization ◽  
Cell Types ◽  
Thymosin Β4 ◽  
Cell Functions ◽  
System Components ◽  
Different Cell Types

The data on properties of thymosin β4, a conserved multifunctional polypeptide of mammals is summarized. Attention has been focused on regulatory activity of thymosin β4 in regard to immune and nervous system components. In these systems thymosin β4 is present in different cell types both stationary and mobile ones. Besides intracellular localization thymosin β4 is also located in extracellular fluids. Inside cells, thymosin β4 has been postulated to regulate actin polymerization as a G-actin-sequestering molecule. But molecular mechanisms of thymosin β4 located extra cells on cell functions remain unclear. The structural-functional organization of thymosin β4 is also discussed. Thymosin β4 is a perspective medicine preparation for the therapy of diseases related to immune and neurological disturbances in patients.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

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