scholarly journals Cables2 Is a Novel Smad2-Regulatory Factor Essential for Early Embryonic Development in Mice

2019 ◽  
Author(s):  
Tra Thi Huong Dinh ◽  
Hiroyoshi Iseki ◽  
Seiya Mizuno ◽  
Saori Iijima-Mizuno ◽  
Yoko Tanimoto ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Expression Patterns ◽  
Physiological Role ◽  
Primitive Streak ◽  
Early Embryonic Development ◽  
Visceral Endoderm ◽  
Tetraploid Complementation ◽  
Mouse Tissues

ABSTRACTCDK5 and Abl enzyme substrate 2 (Cables2), a member of the Cables family that has a C-terminal cyclin box-like domain, is widely expressed in adult mouse tissues. However, the physiological role of Cables2 in vivo is unknown. We show here that Cables2-deficiency causes post-gastrulation embryonic lethality in mice. The mutant embryos progress to gastrulation, but then arrest, and fail to grow. Analysis of gene expression patterns reveals that formation of the anterior visceral endoderm and the primitive streak is impaired in Cables2-deficient embryos. Tetraploid complementation analyses support the critical requirement of Cables2 in both the epiblast and visceral endoderm for progression of embryogenesis. In addition, we show that Cables2 physically interacts with a key mediator of the canonical Nodal pathway, Smad2, and augments its transcriptional activity. These findings provide novel insights into the essential role of Cables2 in the early embryonic development in mice.

scholarly journals Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice

2011 ◽  
Vol 193 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Shinichi Nakagawa ◽  
Takao Naganuma ◽  
Go Shioi ◽  
Tetsuro Hirose
Keyword(s):  
Adult Mouse ◽  
Expression Patterns ◽  
Physiological Role ◽  
Growth Conditions ◽  
Nuclear Bodies ◽  
Cellular Functions ◽  
Mouse Tissues

Nuclei of higher organisms are well structured and have multiple, distinct nuclear compartments or nuclear bodies. Paraspeckles are recently identified mammal-specific nuclear bodies ubiquitously found in most cells cultured in vitro. To investigate the physiological role of paraspeckles, we examined the in vivo expression patterns of two long noncoding RNAs, NEAT1_1 and NEAT1_2, which are essential for the architectural integrity of nuclear bodies. Unexpectedly, these genes were only strongly expressed in a particular subpopulation of cells in adult mouse tissues, and prominent paraspeckle formation was observed only in the cells highly expressing NEAT1_2. To further investigate the cellular functions of paraspeckles, we created an animal model lacking NEAT1 by gene targeting. These knockout mice were viable and fertile under laboratory growth conditions, showing no apparent phenotypes except for the disappearance of paraspeckles. We propose that paraspeckles are nonessential, subpopulation-specific nuclear bodies formed secondary to particular environmental triggers.

scholarly journals Expression and Potential Role of microRNA-29b in Mouse Early Embryo Development

2015 ◽  
Vol 35 (3) ◽  
pp. 1178-1187 ◽  
Author(s):  
Junqiang Zhang ◽  
Ying Wang ◽  
Xiaoguang Liu ◽  
Shenglin Jiang ◽  
Chun Zhao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Embryonic Development ◽  
Dna Methyltransferase ◽  
Biological Function ◽  
Expression Patterns ◽  
Early Embryo ◽  
Early Embryonic Development ◽  
Preimplantation Embryos ◽  
Early Embryos

Background/Aims: MicroRNA-29b (miR29b) has been previously identified in early mouse embryos through miRNA microarray analysis. Recent research has indicated that miR29b participates in DNA methylation by regulating DNA methyltransferase 3a/3b (Dnmt3a/3b) expression. However, the expression pattern and biological function of miR29b in mouse preimplantation embryonic development remain unknown. Methods: In this study, we examined the expression patterns of miR29b and Dnmt3a/3b in mouse early embryos at different developmental stages. Subsequently, expression and localization of DNMT3A/3B protein was analyzed in mouse early embryos by immunofluorescence staining. The biological function of miR29b in mouse early embryos was analyzed by microinjection of commercially available miRNA-specific inhibitors and mimics. Results: Our data showed that Dnmt3a/3b mRNA expression is negatively regulated by miR29b in mouse early embryos. Immunofluorescence analysis revealed that DNMT3A/3B protein expression is predominantly localized within the nucleoplasm of embryos. Alterations to the activity of miR29b could change the DNA methylation levels in mouse preimplantation embryos and lead to a developmental blockade, from the morula to the blastocyst stage. Conclusion: These results indicated a role for the miR29b-Dnmt3a/3b-DNA methylation axis in mouse early embryonic development, and we provide evidence that miR29b is indispensable for mouse early embryonic development. This study contributes to a preliminary understanding of the role of miR29b during mouse embryonic development.

scholarly journals Purinergic Modulation of Interleukin-1β Release from Microglial Cells Stimulated with Bacterial Endotoxin

1997 ◽  
Vol 185 (3) ◽  
pp. 579-582 ◽  
Author(s):  
Davide Ferrari ◽  
Paola Chiozzi ◽  
Simonetta Falzoni ◽  
Stefania Hanau ◽  
Francesco Di  Virgilio
Keyword(s):  
Plasma Membrane ◽  
P2x7 Receptor ◽  
Purinergic Receptor ◽  
Present Report ◽  
Physiological Role ◽  
Bacterial Endotoxin ◽  
Microglial Cells

Microglial cells express a peculiar plasma membrane receptor for extracellular ATP, named P2Z/P2X7 purinergic receptor, that triggers massive transmembrane ion fluxes and a reversible permeabilization of the plasma membrane to hydrophylic molecules of up to 900 dalton molecule weight and eventual cell death (Di Virgilio, F. 1995. Immunol. Today. 16:524–528). The physiological role of this newly cloned (Surprenant, A., F. Rassendren, E. Kawashima, R.A. North and G. Buell. 1996. Science (Wash. DC). 272:735–737) cytolytic receptor is unknown. In vitro and in vivo activation of the macrophage and microglial cell P2Z/P2X7 receptor by exogenous ATP causes a large and rapid release of mature IL-1β. In the present report we investigated the role of microglial P2Z/P2X7 receptor in IL-1β release triggered by LPS. Our data suggest that LPS-dependent IL-1β release involves activation of this purinergic receptor as it is inhibited by the selective P2Z/P2X7 blocker oxidized ATP and modulated by ATP-hydrolyzing enzymes such as apyrase or hexokinase. Furthermore, microglial cells release ATP when stimulated with LPS. LPS-dependent release of ATP is also observed in monocyte-derived human macrophages. It is suggested that bacterial endotoxin activates an autocrine/paracrine loop that drives ATP-dependent IL-1β secretion.

scholarly journals Differences in Ca2+-management between the ventricle of two species of neotropical teleosts: the jeju, Hoplerythrinus unitaeniatus (Spix & Agassiz, 1829), and the acara, Geophagus brasiliensis (Quoy & Gaimard, 1824)

2009 ◽  
Vol 7 (3) ◽  
pp. 471-478 ◽  
Author(s):  
Monica Jones Costa ◽  
Francisco Tadeu Rantin ◽  
Ana Lúcia Kalinin
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Physiological Role ◽  
Stimulation Frequency ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Heart Frequency ◽  
Geophagus Brasiliensis ◽  
Hoplerythrinus Unitaeniatus

This study analyzed the physiological role of the cardiac sarcoplasmic reticulum (SR) of two neotropical teleosts, the jeju, Hoplerythrinus unitaeniatus (Erythrinidae), and the acara, Geophagus brasiliensis (Cichlidae). While the in vivo heart frequency (fH - bpm) of acara (79.6 ± 6.6) was higher than that of the jeju (50.3 ± 2.7), the opposite was observed for the ventricular inotropism (Fc - mN/mm²) at 12 bpm (acara = 28.66 ± 1.86 vs. jeju = 36.09 ± 1.67). A 5 min diastolic pause resulted in a strong potentiation of Fc (≅ 90%) of strips from jeju, which was completely abolished by ryanodine. Ryanodine also resulted in a ≅ 20% decrease in the Fc developed by strips from jeju at both subphysiological (12 bpm) and physiological (in vivo) frequencies. However, this effect of ryanodine reducing the Fc from jeju was completely compensated by adrenaline increments (10-9 and 10-6 M). In contrast, strips from acara were irresponsive to ryanodine, irrespective of the stimulation frequency, and increases in adrenaline concentration (to 10-9 and 10-6 M) further increased Fc. These results reinforce the hypothesis of the functionality of the SR as a common trait in neotropical ostariophysian (as jeju), while in acanthopterygians (as acara) it seems to be functional mainly in 'athletic' species.

scholarly journals Modified Sawhorse Waveform for the Voltammetric Detection of Oxytocin

2022 ◽  
Author(s):  
Favian Liu ◽  
Negar Ghasem Ardabili ◽  
Izaiah Brown ◽  
Harmain Rafi ◽  
Clarice Cook ◽  
...  
Keyword(s):  
Brain Slices ◽  
Physiological Role ◽  
Peptide Hormone ◽  
Protective Effects ◽  
Fast Scan Cyclic Voltammetry ◽  
The Past ◽  
Voltammetric Detection ◽  
Carbon Fiber Microelectrodes

Abstract Carbon fiber microelectrodes (CFMEs) have been used to detect neurotransmitters and other biomolecules using fast-scan cyclic voltammetry (FSCV) for the past few decades. This technique measures neurotransmitters such as dopamine and, more recently, physiologically relevant neuropeptides. Oxytocin, a pleiotropic peptide hormone, is physiologically important for adaptation, development, reproduction, and social behavior. This neuropeptide functions as a stress-coping molecule, an anti-inflammatory agent, and serves as an antioxidant with protective effects especially during adversity or trauma. Here, we measure tyrosine using the Modified Sawhorse Waveform (MSW), enabling enhanced electrode sensitivity for the amino acid and oxytocin peptide. Applying the MSW, decreased surface fouling and enabled codetection with other monoamines. As oxytocin contains tyrosine, the MSW was also used to detect oxytocin. The sensitivity of oxytocin detection was found to be 3.99 ± 0.49 nA/µM, (n=5). Additionally, we demonstrate that applying the MSW on CFMEs allows for real time measurements of exogenously applied oxytocin on rat brain slices. These studies may serve as novel assays for oxytocin detection in a fast, sub-second timescale with possible implications for in vivo measurements and further understanding of the physiological role of oxytocin.

scholarly journals Increased Fitness of Pseudomonas fluorescens Pf0-1 Leucine Auxotrophs in Soil

2008 ◽  
Vol 74 (12) ◽  
pp. 3644-3651 ◽  
Author(s):  
Wook Kim ◽  
Stuart B. Levy
Keyword(s):  
Pseudomonas Fluorescens ◽  
Bacterial Genome ◽  
Physiological Role ◽  
Underlying Mechanism ◽  
Growth Conditions ◽  
Soil Environment ◽  
Fitness Advantage ◽  
Gene Structures

ABSTRACT The annotation process of a newly sequenced bacterial genome is largely based on algorithms derived from databases of previously defined RNA and protein-encoding gene structures. This process generally excludes the possibility that the two strands of a given stretch of DNA can each harbor a gene in an overlapping manner. While the presence of such structures in eukaryotic genomes is considered to be relatively common, their counterparts in prokaryotic genomes are just beginning to be recognized. Application of an in vivo expression technology has previously identified 22 discrete genetic loci in Pseudomonas fluorescens Pf0-1 that were specifically activated in the soil environment, of which 10 were present in an antisense orientation relative to previously annotated genes. This observation led to the hypothesis that the physiological role of overlapping genetic structures may be relevant to growth conditions outside artificial laboratory media. Here, we examined the role of one of the overlapping gene pairs, iiv19 and leuA2, in soil. Although iiv19 was previously demonstrated to be preferentially activated in the soil environment, its absence did not alter the ability of P. fluorescens to colonize or survive in soil. Surprisingly, the absence of the leuA2 gene conferred a fitness advantage in the soil environment when leucine was supplied exogenously. This effect was determined to be independent of the iiv19 gene, and further analyses revealed that amino acid antagonism was the underlying mechanism behind the observed fitness advantage of the bacterium in soil. Our findings provide a potential mechanism for the frequent occurrence of auxotrophic mutants of Pseudomonas spp. in the lungs of cystic fibrosis patients.

Immunomodulation by 17β-estradiol in bivalve hemocytes

2006 ◽  
Vol 291 (3) ◽  
pp. R664-R673 ◽  
Author(s):  
Laura Canesi ◽  
Caterina Ciacci ◽  
Lucia Cecilia Lorusso ◽  
Michele Betti ◽  
Tiziana Guarnieri ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Hydrolytic Enzymes ◽  
Physiological Role ◽  
Estrogen Receptor Α ◽  
Nitrite Accumulation ◽  
No Production ◽  
17Β Estradiol

In mammals, estrogens have dose- and cell-type-specific effects on immune cells and may act as pro- and anti-inflammatory stimuli, depending on the setting. In the bivalve mollusc Mytilus, the natural estrogen 17β-estradiol (E2) has been shown to affect neuroimmune functions. We have investigated the immunomodulatory role of E2 in Mytilus hemocytes, the cells responsible for the innate immune response. E2 at 5–25 nM rapidly stimulated phagocytosis and oxyradical production in vitro; higher concentrations of E2 inhibited phagocytosis. E2-induced oxidative burst was prevented by the nitric oxide (NO) synthase inhibitor NG-monomethyl-l-arginine and superoxide dismutase, indicating involvement of NO and O2−; NO production was confirmed by nitrite accumulation. The effects of E2 were prevented by the antiestrogen tamoxifen and by specific kinase inhibitors, indicating a receptor-mediated mechanism and involvement of p38 MAPK and PKC. E2 induced rapid and transient increases in the phosphorylation state of PKC, as well as of a aCREB-like (cAMP responsive element binding protein) transcription factor, as indicated by Western blot analysis with specific anti-phospho-antibodies. Localization of estrogen receptor-α- and -β-like proteins in hemocytes was investigated by immunofluorescence confocal microscopy. The effects of E2 on immune function were also investigated in vivo at 6 and 24 h in hemocytes of E2-injected mussels. E2 significantly affected hemocyte lysosomal membrane stability, phagocytosis, and extracellular release of hydrolytic enzymes: lower concentrations of E2 resulted in immunostimulation, and higher concentrations were inhibitory. Our data indicate that the physiological role of E2 in immunomodulation is conserved from invertebrates to mammals.

The calcitonin receptor regulates osteocyte lacunae acidity during lactation in mice

2021 ◽  
Vol 249 (1) ◽  
pp. 31-41
Author(s):  
Rachel A Davey ◽  
Michele V Clarke ◽  
Suzanne B Golub ◽  
Patricia K Russell ◽  
Jeffrey D Zajac
Keyword(s):  
Gene Expression ◽  
Direct Action ◽  
Physiological Role ◽  
Calcitonin Receptor ◽  
Ph Indicator ◽  
Osteocyte Lacunae ◽  
Osteocytic Osteolysis ◽  
Indicator Dye

The physiological role of calcitonin, and its receptor, the CTR (or Calcr), has long been debated. We previously provided the first evidence for a physiological role of the CTR to limit maternal bone loss during lactation in mice by a direct action on osteocytes to inhibit osteocytic osteolysis. We now extend these findings to show that CTR gene expression is upregulated two- to three-fold in whole bone of control mice at the end of pregnancy (E18) and lactation (P21) compared to virgin controls. This was associated with an increase in osteoclast activity evidenced by increases in osteoclast surface/bone surface and Dcstamp gene expression. To investigate the mechanism by which the CTR inhibits osteocytic osteolysis, in vivo acidification of the osteocyte lacunae during lactation (P14 days) was assessed using a pH indicator dye. A lower pH was observed in the osteocyte lacunae of lactating Global-CTRKOs compared to controls and was associated with an increase in the gene expression of ATPase H+ transporting V0 subunit D2 (Atp6v0d2) in whole bone of Global-CTRKOs at the end of lacation (P21). To determine whether the CTR is required for the replacement of mineral within the lacunae post-lactation, lacunar area was determined 3 weeks post-weaning. Comparison of the largest 20% of lacunae by area did not differ between Global-CTRKOs and controls post-lactation. These results provide evidence for CTR activation to inhibit osteocytic osteolysis during lactation being mediated by regulating the acidity of the lacunae microenvironment, whilst the CTR is dispensable for replacement of bone mineral within lacunae by osteocytes post-lactation.

A role for the EphA family in the topographic targeting of vomeronasal axons

Development ◽  
2001 ◽  
Vol 128 (6) ◽  
pp. 895-906
Author(s):  
B. Knoll ◽  
K. Zarbalis ◽  
W. Wurst ◽  
U. Drescher
Keyword(s):  
Tyrosine Kinases ◽  
Expression Patterns ◽  
Eph Receptors ◽  
Accessory Olfactory Bulb ◽  
In Vivo Experiments ◽  
Receptor Concentration ◽  
High Ligand

We have investigated the role of the Eph family of receptor tyrosine kinases and their ligands in the establishment of the vomeronasal projection in the mouse. Our data show intriguing differential expression patterns of ephrin-A5 on vomeronasal axons and of EphA6 in the accessory olfactory bulb (AOB), such that axons with high ligand concentration project onto regions of the AOB with high receptor concentration and vice versa. These data suggest a mechanism for development of this projection that is the opposite of the repellent interaction between Eph receptors and ligands observed in other systems. In support of this idea, when given the choice of whether to grow on lanes containing EphA-F(c)/laminin or F(c)/laminin protein (in the stripe assay), vomeronasal axons prefer to grow on EphA-F(c)/laminin. Analysis of ephrin-A5 mutant mice revealed a disturbance of the topographic targeting of vomeronasal axons to the AOB. In summary, these data, which are derived from in vitro and in vivo experiments, indicate an important role of the EphA family in setting up the vomeronasal projection.

Sign in / Sign up

Export Citation Format

Share Document