Increased Apoptosis during Morphogenesis of the Lower Cheek Teeth in Tabby/EDA Mice

2005 ◽  
Vol 84 (3) ◽  
pp. 228-233 ◽  
Author(s):  
T. Boran ◽  
H. Lesot ◽  
M. Peterka ◽  
R. Peterkova
Keyword(s):  
Tooth Development ◽  
Cheek Tooth ◽  
Causal Role ◽  
Wild Type ◽  
3D Reconstructions ◽  
Histological Sections ◽  
Computer Aided ◽  
Tooth Number ◽  
Dental Epithelium

In wild-type (WT) mice, epithelial apoptosis is involved in reducing the embryonic tooth number and the mesial delimitation of the first molar. We investigated whether apoptosis could also be involved in the reduction of tooth number and the determination of anomalous tooth boundaries in tabby (Ta)/EDA mice. Using serial histological sections and computer-aided 3D reconstructions, we investigated epithelial apoptosis in the lower cheek dentition at embryonic days 14.5–17.5. In comparison with WT mice, apoptosis was increased mainly mesially in Ta dental epithelium from day 15.5. This apoptosis showed a similar mesio-distal extent in all 5 morphotypes (Ia,b,c and IIa,b) of Ta dentition and eliminated the first cheek tooth in morphotypes IIa,b. Apoptosis did not appear to play any causal role in positioning inter-dental gaps. Analysis of the present data suggests that the increased apoptosis in Ta mice is a consequence of impaired tooth development caused by a defect in segmentation of dental epithelium.

FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development

Development ◽  
1998 ◽  
Vol 125 (21) ◽  
pp. 4325-4333 ◽  
Author(s):  
M. Bei ◽  
R. Maas
Keyword(s):  
Signaling Pathways ◽  
Tooth Development ◽  
Signaling Molecules ◽  
Dependent Manner ◽  
Wild Type ◽  
Independent Manner ◽  
Dental Lamina ◽  
Bmp4 Expression ◽  
Dental Epithelium ◽  
Tooth Germs

During early tooth development, multiple signaling molecules are expressed in the dental lamina epithelium and induce the dental mesenchyme. One signal, BMP4, has been shown to induce morphologic changes in dental mesenchyme and mesenchymal gene expression via Msx1, but BMP4 cannot substitute for all the inductive functions of the dental epithelium. To investigate the role of FGFs during early tooth development, we examined the expression of epithelial and mesenchymal Fgfs in wild-type and Msx1 mutant tooth germs and tested the ability of FGFs to induce Fgf3 and Bmp4 expression in wild-type and Msx1 mutant dental mesenchymal explants. Fgf8 expression is preserved in Msx1 mutant epithelium while that of Fgf3 is not detected in Msx1 mutant dental mesenchyme. Moreover, dental epithelium as well as beads soaked in FGF1, FGF2 or FGF8 induce Fgf3 expression in dental mesenchyme in an Msx1-dependent manner. These results indicate that, like BMP4, FGF8 constitutes an epithelial inductive signal capable of inducing the expression of downstream signaling molecules in dental mesenchyme via Msx1. However, the BMP4 and FGF8 signaling pathways are distinct. BMP4 cannot induce Fgf3 nor can FGFs induce Bmp4 expression in dental mesenchyme, even though both signaling molecules can induce Msx1 and Msx1 is necessary for Fgf3 and Bmp4 expression in dental mesenchyme. In addition, we have investigated the effects of FGFs and BMP4 on the distal-less homeobox genes Dlx1 and Dlx2 and we have clarified the relationship between Msx and Dlx gene function in the developing tooth. Dlx1,Dlx2 double mutants exhibit a lamina stage arrest in maxillary molar tooth development (Thomas B. L., Tucker A. S., Qiu M., Ferguson C. A., Hardcastle Z., Rubenstein J. L. R. and Sharpe P. T. (1997) Development 124, 4811–4818). Although the maintenance of molar mesenchymal Dlx2 expression at the bud stage is Msx1-dependent, both the maintenance of Dlx1 expression and the initial activation of mesenchymal Dlx1 and Dlx2 expression during the lamina stage are not. Moreover, in contrast to the tooth bud stage arrest observed in Msx1 mutants, Msx1,Msx2 double mutants exhibit an earlier phenotype closely resembling the lamina stage arrest observed in Dlx1,Dlx2 double mutants. These results are consistent with functional redundancy between Msx1 and Msx2 in dental mesenchyme and support a model whereby Msx and Dlx genes function in parallel within the dental mesenchyme during tooth initiation. Indeed, as predicted by such a model, BMP4 and FGF8, epithelial signals that induce differential Msx1 and Msx2 expression in dental mesenchyme, also differentially induce Dlx1 and Dlx2 expression, and do so in an Msx1-independent manner. These results integrate Dlx1, Dlx2 and Fgf3 and Fgf8 into the odontogenic regulatory hierarchy along with Msx1, Msx2 and Bmp4, and provide a basis for interpreting tooth induction in terms of transcription factors which, individually, are necessary but not sufficient for the expression of downstream signals and therefore must act in specific combinations.

scholarly journals A new function of BMP4: dual role for BMP4 in regulation of Sonic hedgehog expression in the mouse tooth germ

Development ◽  
2000 ◽  
Vol 127 (7) ◽  
pp. 1431-1443 ◽  
Author(s):  
Y. Zhang ◽  
Z. Zhang ◽  
X. Zhao ◽  
X. Yu ◽  
Y. Hu ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Sonic Hedgehog ◽  
Tooth Development ◽  
Tooth Germ ◽  
Signaling Molecules ◽  
Limb Bud ◽  
Wild Type ◽  
Morphogenetic Protein ◽  
In The Wild ◽  
Dental Epithelium

The murine tooth development is governed by sequential and reciprocal epithelial-mesenchymal interactions. Multiple signaling molecules are expressed in the developing tooth germ and interact each other to mediate the inductive tissue interactions. Among them are Sonic hedgehog (SHH), Bone Morphogenetic Protein-2 (BMP2) and Bone Morphogenetic Protein-4 (BMP4). We have investigated the interactions between these signaling molecules during early tooth development. We found that the expression of Shh and Bmp2 is downregulated at E12.5 and E13.5 in the dental epithelium of the Msx1 mutant tooth germ where Bmp4 expression is significantly reduced in the dental mesenchyme. Inhibition of BMP4 activity by noggin resulted in repression of Shh and Bmp2 in wild-type dental epithelium. When implanted into the dental mesenchyme of Msx1 mutants, beads soaked with BMP4 protein were able to restore the expression of both Shh and Bmp2 in the Msx1 mutant epithelium. These results demonstrated that mesenchymal BMP4 represents one component of the signal acting on the epithelium to maintain Shh and Bmp2 expression. In contrast, BMP4-soaked beads repressed Shh and Bmp2 expression in the wild-type dental epithelium. TUNEL assay indicated that this suppression of gene expression by exogenous BMP4 was not the result of an increase in programmed cell death in the tooth germ. Ectopic expression of human Bmp4 to the dental mesenchyme driven by the mouse Msx1 promoter restored Shh expression in the Msx1 mutant dental epithelium but repressed Shh in the wild-type tooth germ in vivo. We further demonstrated that this regulation of Shh expression by BMP4 is conserved in the mouse developing limb bud. In addition, Shh expression was unaffected in the developing limb buds of the transgenic mice in which a constitutively active Bmpr-IB is ectopically expressed in the forelimb posterior mesenchyme and throughout the hindlimb mesenchyme, suggesting that the repression of Shh expression by BMP4 may not be mediated by BMP receptor-IB. These results provide evidence for a new function of BMP4. BMP4 can act upstream to Shh by regulating Shh expression in mouse developing tooth germ and limb bud. Taken together, our data provide insight into a new regulatory mechanism for Shh expression, and suggest that this BMP4-mediated pathway in Shh regulation may have a general implication in vertebrate organogenesis.

Designing of Outriggers for the Needs of the Vehicles Stability Testing

2018 ◽  
Vol 875 ◽  
pp. 71-76
Author(s):  
Victor Kryaskov ◽  
Andrey Vashurin ◽  
Anton Tumasov ◽  
Alexey Vasiliev
Keyword(s):  
Coefficient Of Friction ◽  
Computer Aided Design ◽  
Strength Analysis ◽  
Direct Impact ◽  
Stability Testing ◽  
Supporting Surface ◽  
Stability Tests ◽  
Computer Aided ◽  
Aided Design

This paper is dedicated to the issues of designing of outriggers for avoidance of vehicle tilting during its stability tests. An analysis of existing types of outriggers was done by authors as well as legislative requirements on them. The reliable and well-timed operation of outriggers largely depends on the height of their positioning on a vehicle. In order to determine this important parameter a special methodic of determining the tipping angle of the vehicle with the use of computer-aided design (CAD) was composed by authors. The article also contains some main principles of strength analysis of the structure a very important part of which became the necessity of determination of coefficient of friction between the outrigger sliders and the supporting surface. This coefficient has a direct impact on the value of transverse forces appearing at the ends of outrigger beams.

Lif Deficiency Leads to Iron Transportation Dysfunction in Ameloblasts

2021 ◽  
pp. 002203452110119
Author(s):  
L. Fan ◽  
Y.J. Ou ◽  
Y.X. Zhu ◽  
Y.D. Liang ◽  
Y. Zhou ◽  
...  
Keyword(s):  
Tooth Development ◽  
Iron Status ◽  
Acid Resistance ◽  
Blue Staining ◽  
Maturation Stage ◽  
Wild Type ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Stem Cell Pluripotency ◽  
Underlying Mechanisms

Leukemia inhibitory factor (LIF), a member of the interleukin 6 family of cytokines, is involved in skeletal metabolism, blastocyst implantation, and stem cell pluripotency maintenance. However, the role of LIF in tooth development needs to be elucidated. The aim of the present study was to investigate the effect of Lif deficiency on tooth development and to elucidate the functions of Lif during tooth development and the underlying mechanisms. First, it was found that the incisors of Lif-knockout mice had a much whiter color than those of wild-type mice. Although there were no structural abnormalities or defective mineralization according to scanning electronic microscopy and computed tomography analysis, 3-dimensional images showed that the length of incisors was shorter in Lif−/− mice. Microhardness and acid resistance assays showed that the hardness and acid resistance of the enamel surface of Lif−/− mice were decreased compared to those of wild-type mice. In Lif−/− mice, whose general iron status was comparable to that of the control mice, the iron content of the incisors was significantly reduced, as confirmed by energy-dispersive X-ray spectroscopy (EDS) and Prussian blue staining. Histological staining showed that the cell length of maturation-stage ameloblasts was shorter in Lif−/− mice. Likewise, decreased expression of Tfrc and Slc40a1, both of which are crucial proteins for iron transportation, was observed in Lif−/− mice and Lif-knockdown ameloblast lineage cell lines, according to quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Moreover, the upregulation of Tfrc and Slc40a1 induced by Lif stimulation was blocked by Stattic, a signal transducer and activator of transcription 3 (Stat3) signaling inhibitor. These results suggest that Lif deficiency inhibits iron transportation in the maturation-stage ameloblasts, and Lif modulates expression of Tfrc and Slc40a1 through the Stat3 signaling pathway during enamel development.

scholarly journals Evaluation of wild-type MIC distributions as a tool for determination of clinical breakpoints for Mycobacterium tuberculosis

2009 ◽  
Vol 64 (4) ◽  
pp. 786-793 ◽  
Author(s):  
T. Schon ◽  
P. Jureen ◽  
C. G. Giske ◽  
E. Chryssanthou ◽  
E. Sturegard ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Wild Type ◽  
Clinical Breakpoints

scholarly journals Expression Level of Mature miR172 in Wild Type and StSUT4-Silenced Plants of Solanum tuberosum Is Sucrose-Dependent

2021 ◽  
Vol 22 (3) ◽  
pp. 1455
Author(s):  
Varsha Garg ◽  
Aleksandra Hackel ◽  
Christina Kühn
Keyword(s):  
Solanum Tuberosum ◽  
Wild Type ◽  
Potato Plants ◽  
Mature Leaves ◽  
In Vitro Plantlets ◽  
Long Time ◽  
Short Time ◽  
Cut Leaves

In potato plants, the phloem-mobile miR172 is involved in the sugar-dependent transmission of flower and tuber inducing signal transduction pathways and a clear link between solute transport and the induction of flowering and tuberization was demonstrated. The sucrose transporter StSUT4 seems to play an important role in the photoperiod-dependent triggering of both developmental processes, flowering and tuberization, and the phenotype of StSUT4-inhibited potato plants is reminiscent to miR172 overexpressing plants. The first aim of this study was the determination of the level of miR172 in sink and source leaves of StSUT4-silenced as well as StSUT4-overexpressing plants in comparison to Solanum tuberosum ssp. Andigena wild type plants. The second aim was to investigate the effect of sugars on the level of miRNA172 in whole cut leaves, as well as in whole in vitro plantlets that were supplemented with exogenous sugars. Experiments clearly show a sucrose-dependent induction of the level of mature miR172 in short time as well as long time experiments. A sucrose-dependent accumulation of miR172 was also measured in mature leaves of StSUT4-silenced plants where sucrose export is delayed and sucrose accumulates at the end of the light period.

scholarly journals Gating Competence of Constitutively Open CLC-0 Mutants Revealed by the Interaction with a Small Organic Inhibitor

2003 ◽  
Vol 122 (3) ◽  
pp. 295-306 ◽  
Author(s):  
Sonia Traverso ◽  
Laura Elia ◽  
Michael Pusch
Keyword(s):  
Chloride Channels ◽  
Bound State ◽  
Side Chain ◽  
Pore Channel ◽  
Kinetic Properties ◽  
Wild Type ◽  
High Affinity ◽  
Critical Residue ◽  
Fast Gating

Opening of CLC chloride channels is coupled to the translocation of the permeant anion. From the recent structure determination of bacterial CLC proteins in the closed and open configuration, a glutamate residue was hypothesized to form part of the Cl−-sensitive gate. The negatively charged side-chain of the glutamate was suggested to occlude the permeation pathway in the closed state, while opening of a single protopore of the double-pore channel would reflect mainly a movement of this side-chain toward the extracellular pore vestibule, with little rearrangement of the rest of the channel. Here we show that mutating this critical residue (Glu166) in the prototype Torpedo CLC-0 to alanine, serine, or lysine leads to constitutively open channels, whereas a mutation to aspartate strongly slowed down opening. Furthermore, we investigated the interaction of the small organic channel blocker p-chlorophenoxy-acetic acid (CPA) with the mutants E166A and E166S. Both mutants were strongly inhibited by CPA at negative voltages with a >200-fold larger affinity than for wild-type CLC-0 (apparent KD at −140 mV ∼4 μM). A three-state linear model with an open state, a low-affinity and a high-affinity CPA-bound state can quantitatively describe steady-state and kinetic properties of the CPA block. The parameters of the model and additional mutagenesis suggest that the high-affinity CPA-bound state is similar to the closed configuration of the protopore gate of wild-type CLC-0. In the E166A mutant the glutamate side chain that occludes the permeation pathway is absent. Thus, if gating consists only in movement of this side-chain the mutant E166A should not be able to assume a closed conformation. It may thus be that fast gating in CLC-0 is more complex than anticipated from the bacterial structures.

Determination of the Workspace of a Three-Degrees-of-Freedom Parallel Manipulator Using a Three-Dimensional Computer-Aided-Design Software Package and the Concept of Virtual Chains1

2015 ◽  
Vol 8 (2) ◽  
Author(s):  
Andrew Johnson ◽  
Xianwen Kong ◽  
James Ritchie
Keyword(s):  
Computer Aided Design ◽  
Parallel Manipulator ◽  
Degrees Of Freedom ◽  
Graphical Representation ◽  
Three Dimensional ◽  
Parallel Manipulators ◽  
Workspace Analysis ◽  
Computer Aided ◽  
Aided Design

The determination of workspace is an essential step in the development of parallel manipulators. By extending the virtual-chain (VC) approach to the type synthesis of parallel manipulators, this technical brief proposes a VC approach to the workspace analysis of parallel manipulators. This method is first outlined before being illustrated by the production of a three-dimensional (3D) computer-aided-design (CAD) model of a 3-RPS parallel manipulator and evaluating it for the workspace of the manipulator. Here, R, P and S denote revolute, prismatic and spherical joints respectively. The VC represents the motion capability of moving platform of a manipulator and is shown to be very useful in the production of a graphical representation of the workspace. Using this approach, the link interferences and certain transmission indices can be easily taken into consideration in determining the workspace of a parallel manipulator.

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