scholarly journals TNF signaling and macrophages govern fin regeneration in zebrafish larvae

2017 ◽  
Vol 8 (8) ◽  
pp. e2979-e2979 ◽  
Author(s):  
Mai Nguyen-Chi ◽  
Béryl Laplace-Builhé ◽  
Jana Travnickova ◽  
Patricia Luz-Crawford ◽  
Gautier Tejedor ◽  
...  
Keyword(s):  
Cell Activation ◽  
Molecular Mechanisms ◽  
Blastema Cell ◽  
Direct Role ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Blastema Formation ◽  
Zebrafish Larvae ◽  
Macrophage Subset ◽  
Inflammatory Macrophages

Abstract Macrophages are essential for appendage regeneration after amputation in regenerative species. The molecular mechanisms through which macrophages orchestrate blastema formation and regeneration are still unclear. Here, we use the genetically tractable and transparent zebrafish larvae to study the functions of polarized macrophage subsets during caudal fin regeneration. After caudal fin amputation, we show an early and transient accumulation of pro-inflammatory macrophages concomitant with the accumulation of non-inflammatory macrophages which, in contrast to pro-inflammatory macrophages, remain associated to the fin until the end of the regeneration. Chemical and genetic depletion of macrophages suggested that early recruited macrophages that express TNFα are critical for blastema formation. Combining parabiosis and morpholino knockdown strategies, we show that TNFα/TNFR1 signaling pathway is required for the fin regeneration. Our study reveals that TNFR1 has a necessary and direct role in blastema cell activation suggesting that macrophage subset balance provides the accurate TNFα signal to prime regeneration in zebrafish.

scholarly journals NRG1/ErbB signalling controls the dialogue between macrophages and neural crest-derived cells during zebrafish fin regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Béryl Laplace-Builhé ◽  
Audrey Barthelaix ◽  
Said Assou ◽  
Candice Bohaud ◽  
Marine Pratlong ◽  
...  
Keyword(s):  
Neural Crest ◽  
Transgenic Zebrafish ◽  
Critical Function ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Blastema Formation ◽  
Zebrafish Larvae ◽  
Single Cell Rna Sequencing ◽  
Chemical Inhibition ◽  
Macrophage Subsets

AbstractFish species, such as zebrafish (Danio rerio), can regenerate their appendages after amputation through the formation of a heterogeneous cellular structure named blastema. Here, by combining live imaging of triple transgenic zebrafish embryos and single-cell RNA sequencing we established a detailed cell atlas of the regenerating caudal fin in zebrafish larvae. We confirmed the presence of macrophage subsets that govern zebrafish fin regeneration, and identified a foxd3-positive cell population within the regenerating fin. Genetic depletion of these foxd3-positive neural crest-derived cells (NCdC) showed that they are involved in blastema formation and caudal fin regeneration. Finally, chemical inhibition and transcriptomic analysis demonstrated that these foxd3-positive cells regulate macrophage recruitment and polarization through the NRG1/ErbB pathway. Here, we show the diversity of the cells required for blastema formation, identify a discrete foxd3-positive NCdC population, and reveal the critical function of the NRG1/ErbB pathway in controlling the dialogue between macrophages and NCdC.

A2.2 Pro-inflammatory macrophages mediated TNF-alpha signalling is required for caudal fin regenerationin zebrafish larvae

2015 ◽  
Vol 74 (Suppl 1) ◽  
pp. A16.1-A16
Author(s):  
B Laplace-Builhe ◽  
M Nguyen-Chi ◽  
J Travnickova ◽  
P Luz-Crawford ◽  
G Tejedor ◽  
...  
Keyword(s):  
Tnf Alpha ◽  
Caudal Fin ◽  
Zebrafish Larvae ◽  
Inflammatory Macrophages

Inhibitory effects of polystyrene microplastics on caudal fin regeneration in zebrafish larvae

2020 ◽  
Vol 266 ◽  
pp. 114664
Author(s):  
Linqi Gu ◽  
Li Tian ◽  
Gan Gao ◽  
Shaohong Peng ◽  
Jieyu Zhang ◽  
...  
Keyword(s):  
Inhibitory Effects ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Zebrafish Larvae

scholarly journals Inhibition of BMP and FGF signaling prior to wound epithelium formation leads to an aberrant regenerative response in teleost fish Poecilia latipinna

2021 ◽  
Author(s):  
Isha Ranadive ◽  
Sonam Patel ◽  
Siddharth Pai ◽  
Kashmira Khaire ◽  
Suresh Balakrishnan
Keyword(s):  
Cell Death ◽  
Teleost Fish ◽  
The Other ◽  
Fgf Signaling ◽  
Caudal Fin ◽  
Fin Regeneration ◽  
Blastema Formation ◽  
Messenger Molecules ◽  
Wound Epithelium

The BMP and FGF pathways play a pivotal role in the successful regeneration of caudal fin of teleost fish. Individual inhibition of these pathways led to impaired caudal fin regeneration until the pharmacologic inhibitor of FGF (SU5402) and BMP (LDN193189) were metabolized off. Therefore, in the current study both these pathways were inhibited collectively wherein inhibition of BMP and FGF during the wound epithelium formation led to stalling of the process by bringing down the established levels of shh and runx2. In members of the treatment group, it was observed that, each blastema grows crouched rather than linear and the regrown lepidotrichia therefore remain tilted down. Amongst the other irregularities observed, the transition from epithelial to mesenchymal cells was found hindered due to down-regulation of snail and twist, brought about by BMP and FGF inhibition. Compromised expression of Snail and twist deranged the normal levels of cadherins causing disruption in the transition of cells. Lastly, blocking BMP and FGF delayed blastema formation and proliferation due to diminished levels of fgf2, fgf8, fgf10 and bmp6, while casp3 and casp9 levels remained heightened causing accelerated cell death. This study not only highlights the axial role of BMP and FGF pathways in regeneration but also accentuates the collaboration amongst the two. This ingenious coordination of signalling further reinforces the involvement of relaying messenger molecules between these crucial pathways.

Effects of 17α‑ethinylestradiol on caudal fin regeneration in zebrafish larvae

2019 ◽  
Vol 653 ◽  
pp. 10-22 ◽  
Author(s):  
Liwei Sun ◽  
Linqi Gu ◽  
Hana Tan ◽  
Pan Liu ◽  
Gan Gao ◽  
...  
Keyword(s):  
Caudal Fin ◽  
Fin Regeneration ◽  
Zebrafish Larvae

scholarly journals Tim-3 enhances FcεRI-proximal signaling to modulate mast cell activation

2015 ◽  
Vol 212 (13) ◽  
pp. 2289-2304 ◽  
Author(s):  
Binh L. Phong ◽  
Lyndsay Avery ◽  
Tina L. Sumpter ◽  
Jacob V. Gorman ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
T Cells ◽  
Mast Cell ◽  
Signaling Pathways ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Cell Types ◽  
Mast Cell Activation ◽  
Positive Role ◽  
Ample Evidence

T cell (or transmembrane) immunoglobulin and mucin domain protein 3 (Tim-3) has attracted significant attention as a novel immune checkpoint receptor (ICR) on chronically stimulated, often dysfunctional, T cells. Antibodies to Tim-3 can enhance antiviral and antitumor immune responses. Tim-3 is also constitutively expressed by mast cells, NK cells and specific subsets of macrophages and dendritic cells. There is ample evidence for a positive role for Tim-3 in these latter cell types, which is at odds with the model of Tim-3 as an inhibitory molecule on T cells. At this point, little is known about the molecular mechanisms by which Tim-3 regulates the function of T cells or other cell types. We have focused on defining the effects of Tim-3 ligation on mast cell activation, as these cells constitutively express Tim-3 and are activated through an ITAM-containing receptor for IgE (FcεRI), using signaling pathways analogous to those in T cells. Using a variety of gain- and loss-of-function approaches, we find that Tim-3 acts at a receptor-proximal point to enhance Lyn kinase-dependent signaling pathways that modulate both immediate-phase degranulation and late-phase cytokine production downstream of FcεRI ligation.

scholarly journals Targeting pain at its source in sickle cell disease

2018 ◽  
Vol 315 (1) ◽  
pp. R104-R112 ◽  
Author(s):  
Kanika Gupta ◽  
Om Jahagirdar ◽  
Kalpna Gupta
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Somatosensory System ◽  
Organ Damage ◽  
Mast Cell Activation ◽  
Cell Disease ◽  
Central Nervous Systems

Sickle cell disease (SCD) is a genetic disorder associated with hemolytic anemia, end-organ damage, reduced survival, and pain. One of the unique features of SCD is recurrent and unpredictable episodes of acute pain due to vasoocclusive crisis requiring hospitalization. Additionally, patients with SCD often develop chronic persistent pain. Currently, sickle cell pain is treated with opioids, an approach limited by adverse effects. Because pain can start at infancy and continue throughout life, preventing the genesis of pain may be relatively better than treating the pain once it has been evoked. Therefore, we provide insights into the cellular and molecular mechanisms of sickle cell pain that contribute to the activation of the somatosensory system in the peripheral and central nervous systems. These mechanisms include mast cell activation and neurogenic inflammation, peripheral nociceptor sensitization, maladaptation of spinal signals, central sensitization, and modulation of neural circuits in the brain. In this review, we describe potential preventive/therapeutic targets and their targeting with novel pharmacologic and/or integrative approaches to ameliorate sickle cell pain.

scholarly journals When the Blood Hits Your Brain: The Neurotoxicity of Extravasated Blood

2021 ◽  
Vol 22 (10) ◽  
pp. 5132
Author(s):  
Jesse A. Stokum ◽  
Gregory J. Cannarsa ◽  
Aaron P. Wessell ◽  
Phelan Shea ◽  
Nicole Wenger ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Surgical Intervention ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Critical Factor ◽  
Mass Effect ◽  
Direct Role ◽  
Scientific Curiosity ◽  
Clot Removal ◽  
Clinical Literature ◽  
The Central Nervous System

Hemorrhage in the central nervous system (CNS), including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and aneurysmal subarachnoid hemorrhage (aSAH), remains highly morbid. Trials of medical management for these conditions over recent decades have been largely unsuccessful in improving outcome and reducing mortality. Beyond its role in creating mass effect, the presence of extravasated blood in patients with CNS hemorrhage is generally overlooked. Since trials of surgical intervention to remove CNS hemorrhage have been generally unsuccessful, the potent neurotoxicity of blood is generally viewed as a basic scientific curiosity rather than a clinically meaningful factor. In this review, we evaluate the direct role of blood as a neurotoxin and its subsequent clinical relevance. We first describe the molecular mechanisms of blood neurotoxicity. We then evaluate the clinical literature that directly relates to the evacuation of CNS hemorrhage. We posit that the efficacy of clot removal is a critical factor in outcome following surgical intervention. Future interventions for CNS hemorrhage should be guided by the principle that blood is exquisitely toxic to the brain.

scholarly journals A bi-directional dialog between vascular cells and monocytes/macrophages regulates tumor progression

2021 ◽  
Author(s):  
Victor Delprat ◽  
Carine Michiels
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
The Body ◽  
Vascular Cells ◽  
Tumor Associated Macrophage ◽  
Immune Cell Activation ◽  
The Impact

AbstractCancer progression largely depends on tumor blood vessels as well on immune cell infiltration. In various tumors, vascular cells, namely endothelial cells (ECs) and pericytes, strongly regulate leukocyte infiltration into tumors and immune cell activation, hence the immune response to cancers. Recently, a lot of compelling studies unraveled the molecular mechanisms by which tumor vascular cells regulate monocyte and tumor-associated macrophage (TAM) recruitment and phenotype, and consequently tumor progression. Reciprocally, TAMs and monocytes strongly modulate tumor blood vessel and tumor lymphatic vessel formation by exerting pro-angiogenic and lymphangiogenic effects, respectively. Finally, the interaction between monocytes/TAMs and vascular cells is also impacting several steps of the spread of cancer cells throughout the body, a process called metastasis. In this review, the impact of the bi-directional dialog between blood vascular cells and monocytes/TAMs in the regulation of tumor progression is discussed. All together, these data led to the design of combinations of anti-angiogenic and immunotherapy targeting TAMs/monocyte whose effects are briefly discussed in the last part of this review.

A proliferation gradient between proximal and msxb-expressing distal blastema directs zebrafish fin regeneration

Development ◽  
2002 ◽  
Vol 129 (11) ◽  
pp. 2607-2617 ◽  
Author(s):  
Alex Nechiporuk ◽  
Mark T. Keating
Keyword(s):  
High Rate ◽  
Proliferating Cells ◽  
Homogeneous Population ◽  
Fin Regeneration ◽  
New Model ◽  
Blastema Formation ◽  
Phosphohistone H3 ◽  
Slow Cycling ◽  
Early Regeneration ◽  
Regeneration Blastema

Previous studies of zebrafish fin regeneration led to the notion that the regeneration blastema is a homogeneous population of proliferating cells. Here, we show that the blastema consists of two components with markedly distinct proliferation properties. During early blastema formation, proliferating cells are evenly distributed. At the onset of regenerative outgrowth, however, blastemal cells are partitioned into two domains. Proximal blastemal cells proliferate at a high rate, shifting from a median G2 of more than 6 hours to approximately 1 hour. By contrast, the most distal blastemal cells do not proliferate. There is a gradient of proliferation between these extremes. Using bromodeoxyuridine incorporation and anti-phosphohistone H3 labeling, we find a 50-fold difference in proliferation across the gradient that extends approximately 50 μm, or ten cell diameters. We show that during early regeneration, proliferating blastemal cells express msxb, a homeodomain transcriptional repressor. While msxb is widely expressed among proliferating cells during blastema formation, its expression becomes restricted to a small number of non-proliferating, distal blastemal cells during regenerative outgrowth. Bromodeoxyuridine pulse-chase experiments show that distal and proximal blastemal cells are formed from proliferating, msxb-positive blastemal cells, not from preexisting slow-cycling cells. These data support the idea that blastema formation results from dedifferentiation of intraray mesenchymal cells. Based on these findings, we propose a new model of zebrafish fin regeneration in which the function of non-proliferating, msxb-expressing, distal blastemal cells is to specify the boundary of proliferation and provide direction for regenerative outgrowth.

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