scholarly journals ERK signaling controls blastema cell differentiation during planarian regeneration

Development ◽  
2011 ◽  
Vol 138 (12) ◽  
pp. 2417-2427 ◽  
Author(s):  
J. Tasaki ◽  
N. Shibata ◽  
O. Nishimura ◽  
K. Itomi ◽  
Y. Tabata ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Erk Signaling ◽  
Blastema Cell ◽  
Planarian Regeneration

scholarly journals Reactive oxygen species rescue regeneration after silencing the MAPK–ERK signaling pathway in Schmidtea mediterranea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
V. Jaenen ◽  
S. Fraguas ◽  
K. Bijnens ◽  
M. Heleven ◽  
T. Artois ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Light Therapy ◽  
Erk Signaling ◽  
Model Organisms ◽  
Ros Production ◽  
Oxygen Species ◽  
Planarian Regeneration ◽  
Egfr Signaling Pathway

AbstractDespite extensive research on molecular pathways controlling the process of regeneration in model organisms, little is known about the actual initiation signals necessary to induce regeneration. Recently, the activation of ERK signaling has been shown to be required to initiate regeneration in planarians. However, how ERK signaling is activated remains unknown. Reactive Oxygen Species (ROS) are well-known early signals necessary for regeneration in several models, including planarians. Still, the probable interplay between ROS and MAPK/ERK has not yet been described. Here, by interfering with major mediators (ROS, EGFR and MAPK/ERK), we were able to identify wound-induced ROS, and specifically H2O2, as upstream cues in the activation of regeneration. Our data demonstrate new relationships between regeneration-related ROS production and MAPK/ERK activation at the earliest regeneration stages, as well as the involvement of the EGFR-signaling pathway. Our results suggest that (1) ROS and/or H2O2 have the potential to rescue regeneration after MEK-inhibition, either by H2O2-treatment or light therapy, (2) ROS and/or H2O2 are required for the activation of MAPK/ERK signaling pathway, (3) the EGFR pathway can mediate ROS production and the activation of MAPK/ERK during planarian regeneration.

scholarly journals ERK Signaling Controls Innate-like CD8+ T Cell Differentiation via the ELK4 (SAP-1) and ELK1 Transcription Factors

2018 ◽  
Vol 201 (6) ◽  
pp. 1681-1691 ◽  
Author(s):  
Diane Maurice ◽  
Patrick Costello ◽  
Mathew Sargent ◽  
Richard Treisman
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Differentiation ◽  
Erk Signaling

The Downregulation of Onzin Expression and Its Potential Role through Physical and Functional Interaction with PU.1 in AML Cell Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1006-1006
Author(s):  
Ying Huang ◽  
Shao-Fang Wu
Keyword(s):  
Cell Differentiation ◽  
Protein Kinase ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Leukemic Cell ◽  
Erk Signaling ◽  
Human Macrophage ◽  
U937 Cells ◽  
Checkpoint Control ◽  
Empty Vector

Abstract Abstract 1006 Poster Board I-28 Onzin is a small, novel and highly conserved cysteine-rich protein with unique structure and tissue-restricted expression, at the high levels in myeloid, intestine and spleen as well as at lower level in lung. Previous reports indicate that inhibition of endogenous onzin results in a reduced growth rate and an increased sensitivity to apoptotic stimuli, while the enforced expression of onzin in fibroblasts leads to marked apoptotic resistance, loss of G2/M checkpoint control and tumorigenic conversion. However, both the regulation of its expression and its biological role remain greatly elusive. In this study, we provided the first demonstration that onzin expression is significantly downregulated during differentiation induction of acute myeloid leukemic (AML) cell lines and primary cells from AML patients by phorbol 12-myristate 13-acetate (PMA) and all-trans retinoic acid (ATRA). Further, this suppression of onzin expression can also be found in PMA-treated solid tumor cell lines with physiological onzin expression by screening 9 different tumor cells. To explore the potential mechanism of onzin downregulation, next we used PMA as the probe in the following experiment. Applying chemical selective inhibitors and transfected expression of dominant negative mutants or constitutive catalytic form of the related kinases, we showed that Protein kinase C-epsilon (PKCε)-extracellular signal-regulated protein kinase (ERK) signaling axis is required for PMA-induced downregulation of onzin expression. Then, to investigate whether the downregulation of onzin expression is associated with leukemic cell differentiation, the full-length onzin cDNA together with empty vector as a control were respectively transfected into NB4 cells as well as U937 cells by retrovirus infection. NB4 and U937 cells with onzin infection expressed higher level of onzin protein could sufficiently overcome the decrease of endogenous onzin protein induced by PMA. Compared with NB4 and U937 cells with empty vector infection, interestingly, onzin overexpression inhibited PMA- or ATRA-induced cell differentiation, evidenced by CD11b and CD14 expression, NBT assays and morphologic alterations. Finally, to exploit how onzin affects PMA- and ATRA-induced differentiation, we investigated whether onzin interacts with the Runt-related protein 1(Runx1), CCAAT/enhancer-binding protein α (C/EBPα) and PU.1, three important transcriptional factors in hematological cell differentiation. CO-IP results indicate that onzin can effectively interact with PU.1 in 293T and U937 cells, in which the two proteins are respectively ectopically expressed and endogenously expressed, but onzin failed to interact with Runx1 or C/EBPα. Furthermore, we examined the effect of onzin on pM-CSFR-luc (driven by human macrophage colony-stimulating factor receptor promoter containing Runx1, C/EBPα and PU.1 binding sites) activity when transiently transfected with Runx1/CBFα, C/EBPα or PU.1 and onzin alone or together in 293T cells. The results showed that although onzin transefected alone had no effect on M-CSFR-luc activity, onzin can partially but significantly decreased M-CSFR-luc activity driven by PU.1, while the forced expression of onzin also had no effect on the M-CSFR-luc activity driven by Runx1 and C/EBPα. Taken together, this is the first report demonstrating that PMA and ATRA downregulates onzin expression through PKCε-ERK signaling pathway, which favors leukemic cell differentiation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Isolation, Culture, and Differentiation of Blastema Cells from the Regenerating Caudal Fin of Zebrafish

Fishes ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 6 ◽  
Author(s):  
Parameswaran Vijayakumar ◽  
M. Leonor Cancela ◽  
Vincent Laizé
Keyword(s):  
Cell Differentiation ◽  
Primary Cultures ◽  
Cell Types ◽  
Blastema Cell ◽  
Caudal Fin ◽  
Epimorphic Regeneration ◽  
All Trans Retinoic Acid ◽  
Undifferentiated Cells ◽  
Wound Epidermis ◽  
Cost Efficient

The caudal fin of teleost fish has become an excellent system for investigating the mechanisms of epimorphic regeneration. Upon amputation of the caudal fin, a mass of undifferentiated cells, called blastema, proliferate beneath the wound-epidermis and differentiate into various cell types to faithfully restore the missing fin structures. Here we describe a protocol that can be used to isolate and culture blastema cells from zebrafish. Primary cultures were initiated from 36 h post-amputation (hpa) blastema and optimal cell growth was achieved using L-15 medium supplemented with 5% fetal bovine serum in plates either coated with fibronectin or uncoated. After seeding, zebrafish blastema cells formed a uniform culture and exhibited polygonal shapes with prominent nucleus, while various cell types were also observed after few days in culture indicating cell differentiation. Upon treatment with all-trans retinoic acid, zebrafish blastema cells differentiated into neuron-like and oligodendritic-like cells. Immunocytochemistry data also revealed the presence of mesenchymal and neuronal cells. The availability of blastema cell cultures could contribute to a better understanding of epimorphic regeneration by providing a mean to investigate the mechanisms underlying blastema cell differentiation. Furthermore, this protocol is simple, rapid, and cost-efficient, and can be virtually applied to the development of any fish blastema cell culture.

scholarly journals miR-322/miR-503 clusters regulate defective myoblast differentiation in myotonic dystrophy RNA-toxic by targeting Celf1

2021 ◽  
Author(s):  
Wei Dong ◽  
Qian Liu ◽  
Zhi-Chao Wang ◽  
Xing-Xiang Du ◽  
Lei-Lei Liu ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Protein Kinase ◽  
Myotonic Dystrophy ◽  
Intracellular Signaling ◽  
Genetic Disorder ◽  
Mitogen Activated Protein Kinase ◽  
Erk Signaling ◽  
Luciferase Assay ◽  
Myoblast Differentiation ◽  
Myocyte Differentiation

Abstract Myotonic dystrophy (DM) is a genetic disorder featured by muscular dystrophy. It is caused by CUG expansion in the myotonic dystrophy protein kinase gene that leads to aberrant signaling and impaired myocyte differentiation. Many studies have shown that microRNAs are involved in the differentiation process of myoblasts. The purpose of this study was to investigate how the miR-322/miR-503 cluster regulates intracellular signaling to affect cell differentiation. The cell model of DM1 was employed by expressing GFP-CUG200 or CUGBP Elav-like family member 1 (Celf1) in myoblasts. Immunostaining of MF-20 was performed to examine myocyte differentiation. qRT-PCR and western blot were used to determine the levels of Celf1, MyoD, MyoG, Mef2c, miR-322/miR-503, and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling. Dual luciferase assay was performed to validate the interaction between miR-322/miR-503 and Celf1. CUG expansion in myoblasts impaired the cell differentiation, increased the Celf1 level, but it decreased the miR-322/miR-503 levels. miR-322/miR-503 mimics restored the impaired differentiation caused by CUG expansion, while miR-322/miR-503 inhibitors further suppressed. miR-322/miR-503 directly targeted Celf1 and negatively regulated its expression. Knockdown of Celf1 promoted myocyte differentiation. Further, miR-322/miR-503 mimics rescued the impaired differentiation of myocytes caused by CUG expansion or Celf1 overexpression through suppressing of MEK/ERK signaling. miR-322/miR-503 cluster recover the defective myocyte differentiation caused by RNA-toxic via targeting Celf1. Restoring miR-322/miR-503 levels could be an avenue for DM1 therapy.

scholarly journals Signaling gradients in surface dynamics as basis for planarian regeneration

2019 ◽  
Author(s):  
Arnd Scheel ◽  
Angela Stevens ◽  
Christoph Tenbrock
Keyword(s):  
Cell Differentiation ◽  
Stem Cell Differentiation ◽  
Positional Information ◽  
Surface Dynamics ◽  
Dynamic Boundary Conditions ◽  
Planarian Regeneration ◽  
Tissue Surface ◽  
Density Dynamics ◽  
Cutting Experiments ◽  
Positional Control

AbstractWe introduce and analyze a mathematical model for the regeneration of planarian flatworms. This system of differential equations incorporates dynamics of head and tail cells which express positional control genes that in turn translate into localized signals that guide stem cell differentiation. Orientation and positional information is encoded in the dynamics of a long range wnt-related signaling gradient. We motivate our model in relation to experimental data and demonstrate how it correctly reproduces cut and graft experiments. In particular, our system improves on previous models by preserving polarity in regeneration, over orders of magnitude in body size during cutting experiments and growth phases. Our model relies on tristability in cell density dynamics, between head, trunk, and tail. In addition, key to polarity preservation in regeneration, our system includes sensitivity of cell differentiation to gradients of wnt-related signals relative to the tissue surface. This process is particularly relevant in a small tissue layer close to wounds during their healing, and modeled here in a robust fashion through dynamic boundary conditions.

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