scholarly journals Antagonistic interaction between Ezh2 and Arid1a coordinates root patterning and development via Cdkn2a in mouse molars

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Junjun Jing ◽  
Jifan Feng ◽  
Jingyuan Li ◽  
Xia Han ◽  
Jinzhi He ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Root Development ◽  
Physiological Function ◽  
Tooth Root ◽  
Tooth Regeneration ◽  
Jaw Bones ◽  
Antagonistic Interaction ◽  
Tooth Type ◽  
Epigenetic Regulators

Patterning is a critical step during organogenesis and is closely associated with the physiological function of organs. Tooth root shapes are finely tuned to provide precise occlusal support to facilitate the function of each tooth type. However, the mechanism regulating tooth root patterning and development is largely unknown. In this study, we provide the first in vivo evidence demonstrating that Ezh2 in the dental mesenchyme determines patterning and furcation formation during dental root development in mouse molars. Mechanistically, an antagonistic interaction between epigenetic regulators Ezh2 and Arid1a controls Cdkn2a expression in the dental mesenchyme to regulate dental root patterning and development. These findings indicate the importance of balanced epigenetic regulation in determining the tooth root pattern and the integration of roots with the jaw bones to achieve physiological function. Collectively, our study provides important clues about the regulation of organogenesis and has general implications for tooth regeneration in the future.

Sonic Hedgehog Signaling is Important in Tooth Root Development

2006 ◽  
Vol 85 (5) ◽  
pp. 427-431 ◽  
Author(s):  
M. Nakatomi ◽  
I. Morita ◽  
K. Eto ◽  
M.S. Ota
Keyword(s):  
Sonic Hedgehog ◽  
Root Development ◽  
Mutant Cell ◽  
Expression Patterns ◽  
Nuclear Antigen ◽  
Tooth Root ◽  
Shh Signaling ◽  
Hertwig’S Epithelial Root Sheath ◽  
Root Sheath

Hertwig’s epithelial root sheath (HERS) is important for tooth root formation, but the molecular basis for the signaling of root development remains uncertain. We hypothesized that Sonic hedgehog (Shh) signaling is involved in the HERS function, because it mediates epithelial-mesenchymal interactions during embryonic odontogenesis. We examined the gene expression patterns of Shh signaling in murine developing molar roots. Shh and Patched2 transcripts were identified in the HERS, whereas Patched1, Smoothened, and Gli1 were expressed in the proliferative dental mesenchyme in addition to the HERS. To confirm whether Shh signaling physiologically functions in vivo, we analyzed mesenchymal dysplasia ( mes) mice carrying an abnormal C-terminus of the PATCHED1 protein. In the mutant, cell proliferation was repressed around the HERS at 1 wk. Moreover, the molar eruption was disturbed, and all roots were shorter than those in control littermates at 4 wks. These results indicate that Shh signaling is important in tooth root development. Abbreviations used: BrdU, 5-bromo-2′-deoxyuridine; HERS, Hertwig’s epithelial root sheath; NFI-C/CTF, nuclear factor Ic/CAAT box transcription factor; PCNA, proliferating cell nuclear antigen; Ptc, patched; Shh, sonic hedgehog; Smo, smoothened.

scholarly journals Functional Characterization of the mazEF Toxin-Antitoxin System in the Pathogenic Bacterium Agrobacterium tumefaciens

2021 ◽  
Vol 9 (5) ◽  
pp. 1107
Author(s):  
Wonho Choi ◽  
Yoshihiro Yamaguchi ◽  
Ji-Young Park ◽  
Sang-Hyun Park ◽  
Hyeok-Won Lee ◽  
...  
Keyword(s):  
Agrobacterium Tumefaciens ◽  
Physiological Function ◽  
Functional Characterization ◽  
Site Directed Mutagenesis ◽  
In Vitro Assays ◽  
Cell Growth Inhibition ◽  
The Right

Agrobacterium tumefaciens is a pathogen of various plants which transfers its own DNA (T-DNA) to the host plants. It is used for producing genetically modified plants with this ability. To control T-DNA transfer to the right place, toxin-antitoxin (TA) systems of A. tumefaciens were used to control the target site of transfer without any unintentional targeting. Here, we describe a toxin-antitoxin system, Atu0939 (mazE-at) and Atu0940 (mazF-at), in the chromosome of Agrobacterium tumefaciens. The toxin in the TA system has 33.3% identity and 45.5% similarity with MazF in Escherichia coli. The expression of MazF-at caused cell growth inhibition, while cells with MazF-at co-expressed with MazE-at grew normally. In vivo and in vitro assays revealed that MazF-at inhibited protein synthesis by decreasing the cellular mRNA stability. Moreover, the catalytic residue of MazF-at was determined to be the 24th glutamic acid using site-directed mutagenesis. From the results, we concluded that MazF-at is a type II toxin-antitoxin system and a ribosome-independent endoribonuclease. Here, we characterized a TA system in A. tumefaciens whose understanding might help to find its physiological function and to develop further applications.

scholarly journals Unveiling epigenetic regulation in cancer, aging, and rejuvenation with in vivo reprogramming technology

2018 ◽  
Vol 109 (9) ◽  
pp. 2641-2650 ◽  
Author(s):  
Yuko Sogabe ◽  
Hiroshi Seno ◽  
Takuya Yamamoto ◽  
Yasuhiro Yamada
Keyword(s):  
Epigenetic Regulation

scholarly journals Regulation of rat magnocellular neurosecretory system by D-aspartate: evidence for biological role(s) of a naturally occurring free D-amino acid in mammals

2000 ◽  
Vol 167 (2) ◽  
pp. 247-252 ◽  
Author(s):  
H Wang ◽  
H Wolosker ◽  
J Pevsner ◽  
SH Snyder ◽  
DJ Selkoe
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Physiological Function ◽  
Neurosecretory System ◽  
Milk Ejection ◽  
Magnocellular Neurons ◽  
Rat Hypothalamus ◽  
Naturally Occurring

Little evidence is available for the physiological function of D-amino acids in species other than bacteria. Here we demonstrate that naturally occurring freed -aspartate (D-Asp) is present in all magnocellular neurons of rat hypothalamus. The levels of this naturally occurring D-amino acid were elevated during lactation and returned to normal thereafter in the magnocellular neurosecretory system, which produces oxytocin, a hormone responsible for milk ejection during lactation. Intraperitoneal injections of D-Asp reproducibly increased oxytocin gene expression and decreased the concentration of circulating oxytocin in vivo. Similar changes were observed in the vasopressin system. These results provide evidence for the role(s) of naturally occurring free D-Asp in mammalian physiology. The findings argue against the conventional concept that only L-stereoisomers of amino acids are functional in higher species.

scholarly journals Direct biologically based biosensing of dynamic physiological function

2001 ◽  
Vol 280 (5) ◽  
pp. H2006-H2010 ◽  
Author(s):  
David J. Christini ◽  
Jeff Walden ◽  
Jay M. Edelberg
Keyword(s):  
Real Time ◽  
Cardiac Tissue ◽  
Physiological Function ◽  
Physiological Activity ◽  
Functional Integration ◽  
Dynamic Regulation ◽  
Excitable Tissue ◽  
Alternative Approach

Dynamic regulation of biological systems requires real-time assessment of relevant physiological needs. Biosensors, which transduce biological actions or reactions into signals amenable to processing, are well suited for such monitoring. Typically, in vivo biosensors approximate physiological function via the measurement of surrogate signals. The alternative approach presented here would be to use biologically based biosensors for the direct measurement of physiological activity via functional integration of relevant governing inputs. We show that an implanted excitable-tissue biosensor (excitable cardiac tissue) can be used as a real-time, integrated bioprocessor to analyze the complex inputs regulating a dynamic physiological variable (heart rate). This approach offers the potential for long-term biologically tuned quantification of endogenous physiological function.

scholarly journals Generation and Characterization of Smac/DIABLO-Deficient Mice

2002 ◽  
Vol 22 (10) ◽  
pp. 3509-3517 ◽  
Author(s):  
Hitoshi Okada ◽  
Woong-Kyung Suh ◽  
Jianping Jin ◽  
Minna Woo ◽  
Chunying Du ◽  
...  
Keyword(s):  
Physiological Function ◽  
Es Cells ◽  
Embryonic Stem ◽  
Caspase Activation ◽  
Proapoptotic Protein ◽  
Apoptosis Proteins ◽  
Deficient Mice

ABSTRACT The mitochondrial proapoptotic protein Smac/DIABLO has recently been shown to potentiate apoptosis by counteracting the antiapoptotic function of the inhibitor of apoptosis proteins (IAPs). In response to apoptotic stimuli, Smac is released into the cytosol and promotes caspase activation by binding to IAPs, thereby blocking their function. These observations have suggested that Smac is a new regulator of apoptosis. To better understand the physiological function of Smac in normal cells, we generated Smac-deficient (Smac−/− ) mice by using homologous recombination in embryonic stem (ES) cells. Smac−/− mice were viable, grew, and matured normally and did not show any histological abnormalities. Although the cleavage in vitro of procaspase-3 was inhibited in lysates of Smac−/− cells, all types of cultured Smac−/− cells tested responded normally to all apoptotic stimuli applied. There were also no detectable differences in Fas-mediated apoptosis in the liver in vivo. Our data strongly suggest the existence of a redundant molecule or molecules capable of compensating for a loss of Smac function.

scholarly journals Epigenetic Regulation of Cardiac Neural Crest Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Shun Yan ◽  
Jin Lu ◽  
Kai Jiao
Keyword(s):  
Neural Crest ◽  
Epigenetic Regulation ◽  
Heart Development ◽  
Congenital Heart ◽  
Heart Diseases ◽  
Heart Defects ◽  
Neural Crest Cells ◽  
Abnormal Development ◽  
Cardiac Neural Crest ◽  
Epigenetic Regulators

The cardiac neural crest cells (cNCCs) is a transient, migratory cell population that contribute to the formation of major arteries and the septa and valves of the heart. Abnormal development of cNCCs leads to a spectrum of congenital heart defects that mainly affect the outflow region of the hearts. Signaling molecules and transcription factors are the best studied regulatory events controlling cNCC development. In recent years, however, accumulated evidence supports that epigenetic regulation also plays an important role in cNCC development. Here, we summarize the functions of epigenetic regulators during cNCC development as well as cNCC related cardiovascular defects. These factors include ATP-dependent chromatin remodeling factors, histone modifiers and DNA methylation modulators. In many cases, mutations in the genes encoding these factors are known to cause inborn heart diseases. A better understanding of epigenetic regulators, their activities and their roles during heart development will ultimately contribute to the development of new clinical applications for patients with congenital heart disease.

Sign in / Sign up

Export Citation Format

Share Document