Mps1 defines a proximal blastemal proliferative compartment essential for zebrafish fin regeneration

Development ◽  
2002 ◽  
Vol 129 (22) ◽  
pp. 5141-5149
Author(s):  
Kenneth D. Poss ◽  
Alex Nechiporuk ◽  
Ann M. Hillam ◽  
Stephen L. Johnson ◽  
Mark T. Keating

One possible reason why regeneration remains enigmatic is that the dominant organisms used for studying regeneration are not amenable to genetic approaches. We mutagenized zebrafish and screened for temperature-sensitive defects in adult fin regeneration. The nightcap mutant showed a defect in fin regeneration that was first apparent at the onset of regenerative outgrowth. Positional cloning revealed that nightcapencodes the zebrafish orthologue of mps1, a kinase required for the mitotic checkpoint. mps1 expression was specifically induced in the proximal regeneration blastema, a group of cells that normally proliferate intensely during outgrowth. The nightcap mutation caused severe defects in these cells. However, msxb-expressing blastemal cells immediately distal to this proliferative region did not induce mps1and were retained in mutants. These results indicate that the proximal blastema comprises an essential subpopulation of the fin regenerate defined by the induction and function of Mps1. Furthermore, we show that molecular mechanisms of complex tissue regeneration can now be dissected using zebrafish genetics.


2021 ◽  
Vol 9 ◽  
Author(s):  
Vivien Bothe ◽  
Igor Schneider ◽  
Nadia B. Fröbisch

Regeneration, the replacement of body parts in a living animal, has excited scientists for centuries and our knowledge of vertebrate appendage regeneration has increased significantly over the past decades. While the ability of amniotes to regenerate body parts is very limited, members of other vertebrate clades have been shown to have rather high regenerative capacities. Among tetrapods (four-limbed vertebrates), only salamanders show unparalleled capacities of epimorphic tissue regeneration including replacement of organ and body parts in an apparently perfect fashion. The closest living relatives of Tetrapoda, the lungfish, show regenerative abilities that are comparable to those of salamanders and recent studies suggest that these high regenerative capacities may indeed be ancestral for bony fish (osteichthyans) including tetrapods. While great progress has been made in recent years in understanding the cellular and molecular mechanisms deployed during appendage regeneration, comparatively few studies have investigated gross morphological and histological features of regenerated fins and limbs. Likewise, rather little is known about how fin regeneration compares morphologically to salamander limb regeneration. In this study, we investigated the morphology and histology of regenerated fins in all three modern lungfish families. Data from histological serial sections, 3D reconstructions, and x-ray microtomography scans were analyzed to assess morphological features, quality and pathologies in lungfish fin regenerates. We found several anomalies resulting from imperfect regeneration in regenerated fins in all investigated lungfish species, including fusion of skeletal elements, additional or fewer elements, and distal branching. The similarity of patterns in regeneration abnormalities compared to salamander limb regeneration lends further support to the hypothesis that high regenerative capacities are plesiomorphic for sarcopterygians.





2018 ◽  
Author(s):  
Stacy A. Malaker ◽  
Kayvon Pedram ◽  
Michael J. Ferracane ◽  
Elliot C. Woods ◽  
Jessica Kramer ◽  
...  

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>



2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.



2021 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
Laeya Baldini ◽  
Bruno Charpentier ◽  
Stéphane Labialle

Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity.



2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.



2021 ◽  
pp. 1-5
Author(s):  
Shivani Sachdeva ◽  
Harish Saluja ◽  
Amit Mani ◽  
M.B. Phadnaik

INTRODUCTION: Novel concept known as tissue engineering is for the betterment of human. The use of much advanced molecular science and cell biology in processing the tissues to regenerate even after the loss of inborn tendency of pluripotent cells to multiply is possible by this new therapy. CONTENT: Periodontal tissue regeneration in both height and function is attributed to a complete recovery of the periodontal structures, that is, the formation of alveolar bone, a new connective attachment through collagen fibers as well as functionally oriented on the newly formed cementum is regeneration. Cell based therapies including tissue regeneration is an alternative approach for the regeneration of tissues damaged by disease or trauma. SUMMARY: Though tissue engineering requires the fundamentals of all the three keys namely genomics, proteomics and biometrics to give the solutions to biological problems appearing in dentistry as well as medical sciences.



Author(s):  
Yiping Hu ◽  
Juan He ◽  
Lianhua He ◽  
Bihua Xu ◽  
Qingwen Wang

AbstractTransforming growth factor-β (TGF-β) plays a critical role in the pathological processes of various diseases. However, the signaling mechanism of TGF-β in the pathological response remains largely unclear. In this review, we discuss advances in research of Smad7, a member of the I-Smads family and a negative regulator of TGF-β signaling, and mainly review the expression and its function in diseases. Smad7 inhibits the activation of the NF-κB and TGF-β signaling pathways and plays a pivotal role in the prevention and treatment of various diseases. Specifically, Smad7 can not only attenuate growth inhibition, fibrosis, apoptosis, inflammation, and inflammatory T cell differentiation, but also promotes epithelial cells migration or disease development. In this review, we aim to summarize the various biological functions of Smad7 in autoimmune diseases, inflammatory diseases, cancers, and kidney diseases, focusing on the molecular mechanisms of the transcriptional and posttranscriptional regulation of Smad7.



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