scholarly journals BMP signaling is essential for sustaining proximo-distal progression in regenerating axolotl limbs

Development ◽  
2020 ◽  
Vol 147 (14) ◽  
pp. dev170829
Author(s):  
Etienne Vincent ◽  
Eric Villiard ◽  
Fadi Sader ◽  
Sabin Dhakal ◽  
Benjamin H. Kwok ◽  
...  
Keyword(s):  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Bmp Signaling ◽  
Regeneration Process ◽  
Time Points ◽  
Number Of Genes ◽  
Patterning Genes

ABSTRACTAmputation of a salamander limb triggers a regeneration process that is perfect. A limited number of genes have been studied in this context and even fewer have been analyzed functionally. In this work, we use the BMP signaling inhibitor LDN193189 on Ambystoma mexicanum to explore the role of BMPs in regeneration. We find that BMP signaling is required for proper expression of various patterning genes and that its inhibition causes major defects in the regenerated limbs. Fgf8 is downregulated when BMP signaling is blocked, but ectopic injection of either human or axolotl protein did not rescue the defects. By administering LDN193189 treatments at different time points during regeneration, we show clearly that limb regeneration progresses in a proximal to distal fashion. This demonstrates that BMPs play a major role in patterning of regenerated limbs and that regeneration is a progressive process like development.

Citral, an inhibitor of retinoic acid synthesis, modifies pattern formation during limb regeneration in the axolotl Ambystoma mexicanum

1999 ◽  
Vol 77 (11) ◽  
pp. 1835-1837 ◽  
Author(s):  
Steven R Scadding
Keyword(s):  
Retinoic Acid ◽  
Pattern Formation ◽  
Limb Regeneration ◽  
Acid Synthesis ◽  
Ambystoma Mexicanum

While the effects of exogenous retinoids on amphibian limb regeneration have been studied extensively, the role of endogenous retinoids is not clear. Hence, I wished to investigate the role of endogenous retinoic acid during axolotl limb regeneration. Citral is a known inhibitor of retinoic acid synthesis. Thus, I treated regenerating limbs of the larval axolotl Ambystoma mexicanum with citral. The result of this inhibition of retinoic acid synthesis was that limb regeneration became extremely irregular and hypomorphic, with serious pattern defects, or was inhibited altogether. I conclude that endogenous retinoic acid plays an important role in pattern formation during limb regeneration.

scholarly journals Efficient gene knockin in axolotl and its use to test the role of satellite cells in limb regeneration

2017 ◽  
Vol 114 (47) ◽  
pp. 12501-12506 ◽  
Author(s):  
Ji-Feng Fei ◽  
Maritta Schuez ◽  
Dunja Knapp ◽  
Yuka Taniguchi ◽  
David N. Drechsel ◽  
...  
Keyword(s):  
Reporter Gene ◽  
Satellite Cells ◽  
Limb Regeneration ◽  
Independent Method ◽  
Ambystoma Mexicanum ◽  
Cell Populations ◽  
Genetic Tool ◽  
Efficient Gene ◽  
Unique Model

Salamanders exhibit extensive regenerative capacities and serve as a unique model in regeneration research. However, due to the lack of targeted gene knockin approaches, it has been difficult to label and manipulate some of the cell populations that are crucial for understanding the mechanisms underlying regeneration. Here we have established highly efficient gene knockin approaches in the axolotl (Ambystoma mexicanum) based on the CRISPR/Cas9 technology. Using a homology-independent method, we successfully inserted both the Cherry reporter gene and a larger membrane-tagged Cherry-ERT2-Cre-ERT2 (∼5-kb) cassette into axolotl Sox2 and Pax7 genomic loci. Depending on the size of the DNA fragments for integration, 5–15% of the F0 transgenic axolotl are positive for the transgene. Using these techniques, we have labeled and traced the PAX7-positive satellite cells as a major source contributing to myogenesis during axolotl limb regeneration. Our work brings a key genetic tool to molecular and cellular studies of axolotl regeneration.

Gap junctions in the limb regeneration blastema of the axolotl, Ambystoma mexicanum, are not distributed uniformly and are regulated by retinoic acid

1999 ◽  
Vol 77 (6) ◽  
pp. 902-909
Author(s):  
Leigh-Anne D Miller ◽  
Melissa L Farquhar ◽  
John S Greenwood ◽  
Steven R Scadding
Keyword(s):  
Retinoic Acid ◽  
Gap Junctions ◽  
Limb Regeneration ◽  
Ambystoma Mexicanum ◽  
Limb Bud ◽  
Gap Junctional Communication ◽  
Junctional Communication ◽  
Gap Junctional ◽  
Regeneration Blastema

Gap junctions are thought to play a role in pattern formation during limb development and regeneration by controlling the movement of small regulatory molecules between cells. An anteroposterior gradient of gap junctional communication that is higher posteriorly has been reported in the developing chick limb bud. In both the developing chick limb bud and the amphibian regenerating limb, an anteroposterior retinoic acid gradient is present, and this is also higher posteriorly. On the basis of these observations, we decided to examine the role of gap junctional communication in the regenerating amphibian limb. Gap junctions were observed in both the axolotl, Ambystoma mexicanum, limb regeneration blastema and cardiac tissue (as a positive control), using immunohistochemical labelling and laser scanning confocal microscopy. The scrape-loading/dye transfer technique for tracing the movement of a gap junction permeable dye, Lucifer yellow, showed that in blastemal epidermis there were nonuniform distributions of gap junctions in both the dorsoventral and anteroposterior axes of the blastema. Retinoic acid was found to increase gap junctional permeability in blastemal epidermis 48 h after injection and in blastemal mesenchyme 76 h after injection. The potential role of gap junctions during pattern formation in limb regeneration is discussed based on these results.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

Epigenetic Regulator Signatures in Regenerative Capacity

2019 ◽  
Vol 14 (7) ◽  
pp. 598-606
Author(s):  
Sarah Albogami
Keyword(s):  
Epigenetic Regulation ◽  
Animal Species ◽  
Current Knowledge ◽  
Regeneration Process ◽  
Body Parts ◽  
Lysine Methylation ◽  
Regenerative Capacity ◽  
Biological Phenomena ◽  
Epigenetic Regulator

Background:: Regeneration is the process by which body parts lost as a result of injury are replaced, as observed in certain animal species. The root of regenerative differences between organisms is still not very well understood; if regeneration merely recycles developmental pathways in the adult form, why can some animals regrow organs whereas others cannot? In the regulation of the regeneration process as well as other biological phenomena, epigenetics plays an essential role. Objective:: This review aims to demonstrate the role of epigenetic regulators in determining regenerative capacity. Results:: In this review, we discuss the basis of regenerative differences between organisms. In addition, we present the current knowledge on the role of epigenetic regulation in regeneration, including DNA methylation, histone modification, lysine methylation, lysine methyltransferases, and the SET1 family. Conclusion:: An improved understanding of the regeneration process and the epigenetic regulation thereof through the study of regeneration in highly regenerative species will help in the field of regenerative medicine in future.

scholarly journals Model-based evaluation of school- and non-school-related measures to control the COVID-19 pandemic

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ganna Rozhnova ◽  
Christiaan H. van Dorp ◽  
Patricia Bruijning-Verhagen ◽  
Martin C. J. Bootsma ◽  
Janneke H. H. M. van de Wijgert ◽  
...  
Keyword(s):  
Reproduction Number ◽  
Additional Benefit ◽  
Transmission Model ◽  
Time Points ◽  
School Based ◽  
Admission Data ◽  
Age Structured ◽  
The Impact ◽  
Pandemic Wave

AbstractThe role of school-based contacts in the epidemiology of SARS-CoV-2 is incompletely understood. We use an age-structured transmission model fitted to age-specific seroprevalence and hospital admission data to assess the effects of school-based measures at different time points during the COVID-19 pandemic in the Netherlands. Our analyses suggest that the impact of measures reducing school-based contacts depends on the remaining opportunities to reduce non-school-based contacts. If opportunities to reduce the effective reproduction number (Re) with non-school-based measures are exhausted or undesired and Re is still close to 1, the additional benefit of school-based measures may be considerable, particularly among older school children. As two examples, we demonstrate that keeping schools closed after the summer holidays in 2020, in the absence of other measures, would not have prevented the second pandemic wave in autumn 2020 but closing schools in November 2020 could have reduced Re below 1, with unchanged non-school-based contacts.

scholarly journals The Role of BMP Signaling in Osteoclast Regulation

2021 ◽  
Vol 9 (3) ◽  
pp. 24
Author(s):  
Brian Heubel ◽  
Anja Nohe
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Diseases ◽  
Bmp Signaling ◽  
Bone Homeostasis ◽  
Direct Stimulation ◽  
Federal Drug Administration ◽  
Bmp Pathway ◽  
Stimulation Of

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.

Characteristics of educators’ talk about decontextualised events

2020 ◽  
Vol 45 (4) ◽  
pp. 362-376
Author(s):  
Rebecca Andrews ◽  
Penny Van Bergen
Keyword(s):  
Communication Skills ◽  
Future Event ◽  
Time Points ◽  
Long Day ◽  
Future Events ◽  
Day Care Centres ◽  
Highly Correlated ◽  
Children’S Thinking ◽  
Sydney Australia

This study investigated the characteristics of educators’ talk about decontextualised events with young children in seven early childhood long day care centres in Sydney, Australia. Educators were partnered with up to six children aged between 27 and 60 months. Across two time points, 85 educator–child dyads discussed past and future events. Educators’ use of questions, contextual statements, evaluations and prompts and children’s use of questions, open-ended responses, yes-no responses and spontaneous information statements were examined. Educators’ evaluative statements were highly correlated and educators’ questions were moderately correlated with children’s open-ended responses in past event conversations. Educators’ evaluative statements were highly correlated with children’s open-ended responses in future event conversations and were the only significant predictor for children’s talk. Given the important role of educators in scaffolding children’s thinking and communication skills, the recommended strategies for educators’ talk in decontextualised conversations include: sharing the conversational load, making frequent contextual statements and following the child’s lead/interests.

scholarly journals Horizontal Gene Transfer Involving Chloroplasts

2021 ◽  
Vol 22 (9) ◽  
pp. 4484
Author(s):  
Ewa Filip ◽  
Lidia Skuza
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Driving Force ◽  
Genetic Material ◽  
Adaptive Significance ◽  
Chloroplast Genomes ◽  
Organelle Genomes ◽  
Number Of Genes ◽  
Cellular Compartments

Horizontal gene transfer (HGT)- is defined as the acquisition of genetic material from another organism. However, recent findings indicate a possible role of HGT in the acquisition of traits with adaptive significance, suggesting that HGT is an important driving force in the evolution of eukaryotes as well as prokaryotes. It has been noted that, in eukaryotes, HGT is more prevalent than originally thought. Mitochondria and chloroplasts lost a large number of genes after their respective endosymbiotic events occurred. Even after this major content loss, organelle genomes still continue to lose their own genes. Many of these are subsequently acquired by intracellular gene transfer from the original plastid. The aim of our review was to elucidate the role of chloroplasts in the transfer of genes. This review also explores gene transfer involving mitochondrial and nuclear genomes, though recent studies indicate that chloroplast genomes are far more active in HGT as compared to these other two DNA-containing cellular compartments.

scholarly journals WNT/β-catenin-suppressed FTO expression increases m6A of c-Myc mRNA to promote tumor cell glycolysis and tumorigenesis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xueying Yang ◽  
Fei Shao ◽  
Dong Guo ◽  
Wei Wang ◽  
Juhong Wang ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Promoter Region ◽  
Critical Role ◽  
Mrna Translation ◽  
Poor Survival ◽  
Subsequent Increase ◽  
Critical Pathways ◽  
Number Of Genes ◽  
Promote Tumor Cell

AbstractFTO removes the N6-methyladenosine (m6A) modification from genes and plays a critical role in cancer development. However, the mechanisms underlying the regulation of FTO and its subsequent impact on the regulation of the epitranscriptome remain to be further elucidated. Here, we demonstrate that FTO expression is downregulated and inversely correlated with poor survival of lung adenocarcinoma patients. Mechanistically, Wnt signaling induces the binding of EZH2 to β-catenin. This protein complex binds to the LEF/TCF-binding elements at the promoter region of FTO, where EZH2 enhances H3K27me3 and inhibits FTO expression. Downregulated FTO expression substantially enhances the m6A levels in the mRNAs of a large number of genes in critical pathways, particularly metabolic pathway genes, such as MYC. Enhanced m6A levels on MYC mRNA recruit YTHDF1 binding, which promotes MYC mRNA translation and a subsequent increase in glycolysis and proliferation of tumor cells and tumorigenesis. Our findings uncovered a critical mechanism of epitranscriptome regulation by Wnt/β-catenin-mediated FTO downregulation and underscored the role of m6A modifications of MYC mRNA in regulating tumor cell glycolysis and growth.

Sign in / Sign up

Export Citation Format

Share Document