scholarly journals Thyroid hormone regulated genes in cerebral cortex development

2017 ◽  
Vol 232 (2) ◽  
pp. R83-R97 ◽  
Author(s):  
Juan Bernal
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormones ◽  
Fetal Development ◽  
Cell Types ◽  
Control Of Gene Expression ◽  
Cellular Targets ◽  
Cerebral Cortex Development ◽  
Subplate Neurons ◽  
Genes Encoding

The physiological and developmental effects of thyroid hormones are mainly due to the control of gene expression after interaction of T3 with the nuclear receptors. To understand the role of thyroid hormones on cerebral cortex development, knowledge of the genes regulated by T3 during specific stages of development is required. In our laboratory, we previously identified genes regulated by T3 in primary cerebrocortical cells in culture. By comparing these data with transcriptomics of purified cell types from the developing cortex, the cellular targets of T3 can be identified. In addition, many of the genes regulated transcriptionally by T3 have defined roles in cortex development, from which the role of T3 can be derived. This review analyzes the specific roles of T3-regulated genes in the different stages of cortex development within the physiological frame of the developmental changes of thyroid hormones and receptor concentrations in the human cerebral cortex during fetal development. These data indicate an increase in the sensitivity to T3 during the second trimester of fetal development. The main cellular targets of T3 appear to be the Cajal-Retzius and the subplate neurons. On the other hand, T3 regulates transcriptionally genes encoding extracellular matrix proteins, involved in cell migration and the control of diverse signaling pathways.

scholarly journals Thyroid Hormone Action in Cerebellum and Cerebral Cortex Development

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Fabrice Chatonnet ◽  
Frédéric Picou ◽  
Teddy Fauquier ◽  
Frédéric Flamant
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Glial Cell ◽  
Nuclear Receptors ◽  
Target Genes ◽  
Cell Types ◽  
Hormone Action ◽  
Cerebral Cortex Development ◽  
Thyroid Hormone Action

Thyroid hormones (TH, including the prohormone thyroxine (T4) and its active deiodinated derivative 3,,5-triiodo-L-thyronine (T3)) are important regulators of vertebrates neurodevelopment. Specific transporters and deiodinases are required to ensure T3 access to the developing brain. T3 activates a number of differentiation processes in neuronal and glial cell types by binding to nuclear receptors, acting directly on transcription. Only few T3 target genes are currently known. Deeper investigations are urgently needed, considering that some chemicals present in food are believed to interfere with T3 signaling with putative neurotoxic consequences.

scholarly journals Role of Late Maternal Thyroid Hormones in Cerebral Cortex Development: An Experimental Model for Human Prematurity

2009 ◽  
Vol 20 (6) ◽  
pp. 1462-1475 ◽  
Author(s):  
P. Berbel ◽  
D. Navarro ◽  
E. Auso ◽  
E. Varea ◽  
A. E. Rodriguez ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormones ◽  
Experimental Model ◽  
Cerebral Cortex Development ◽  
Maternal Thyroid

Abstract O.16: Comprehensive Genotyping Of The FCGR2/3 Locus Reveals A Novel Association Of FCGR2C-ORF With Susceptibility To Kawasaki Disease

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Taco W Kuijpers ◽  
Carline E Tacke ◽  
Sietse Q Nagelkerke ◽  
Willemijn B Breunis ◽  
Long T Hoang ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Myeloid Cell ◽  
Cell Types ◽  
Copy Number Variations ◽  
Nucleotide Polymorphisms ◽  
Homologous Genes ◽  
Genes Encoding ◽  
Novel Association ◽  
Family Based

The human FCGR2/3 locus contains highly homologous genes encoding the five major receptors for IgG (Fc-gamma receptors, FcγRs). In two prior GWAS on Kawasaki disease (KD), a SNP in FCGR2A (131H>R; rs1801274) was identified to be associated with disease susceptibility. However, the FCGR2/3 locus contains multiple single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), which were not covered by the detection platforms used in the GWAS. In this study we therefore focused on further fine-mapping of this locus to investigate the association of the different genetic variations with KD susceptibility. A highly accurate and validated multiplex ligation-dependent probe amplification (MLPA) assay was used to analyze all functionally relevant SNPs and CNVs within this locus. In a genetic association study involving case-control and family-based testing with 1028 patients with KD, the previous finding of FCGR2A-131H as a susceptibility marker for KD was confirmed (OR 1.16; 95%CI 1.08-1.32, meta-P = 0.01). In addition, we found a novel significant association of the FCGR2C-ORF haplotype with susceptibility to KD (OR 1.34; 95% confidence interval 1.11-1.62, meta-P = 0.003). FCGR2C-ORF leads to the expression of an extra, functionally activating FcγR (i.e. FcγRIIc) on myeloid cell types and NK cells. Being absent in Asian individuals, the FCGR2C-ORF haplotype only contributed to KD susceptibility in European subjects, independent of the established association with FCGR2A-H131R. We did not find any significant association of CNV of the locus with susceptibility to KD. Our data point to an important role of the activating FcγRs in KD pathology. We hypothesize that the identified functional SNPs might alter the balance between the activating and inhibitory FcγRs leading to unbalanced inflammation and KD.

scholarly journals Transforming growth factor–β in tissue fibrosis

2020 ◽  
Vol 217 (3) ◽  
Author(s):  
Nikolaos G. Frangogiannis
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Cellular Targets ◽  
Extracellular Matrix Molecules ◽  
Interacting Networks

TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β–driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.

scholarly journals Critical Role of Types 2 and 3 Deiodinases in the Negative Regulation of Gene Expression by T3 in the Mouse Cerebral Cortex

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2919-2928 ◽  
Author(s):  
Arturo Hernandez ◽  
Beatriz Morte ◽  
Mónica M. Belinchón ◽  
Ainhoa Ceballos ◽  
Juan Bernal
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Control Of Gene Expression ◽  
High Doses ◽  
And Function ◽  
Type 3

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T3 to nuclear receptors. Brain T3 concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T4 and T3. We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T3 led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T3 treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T3 action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T3 concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

scholarly journals The role of α-E-catenin in cerebral cortex development: radial glia specific effect on neuronal migration

2014 ◽  
Vol 8 ◽  
Author(s):  
Marie-Theres Schmid ◽  
Franziska Weinandy ◽  
Michaela Wilsch-Bräuninger ◽  
Wieland B. Huttner ◽  
Silvia Cappello ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Migration ◽  
Radial Glia ◽  
Specific Effect ◽  
Cerebral Cortex Development

scholarly journals A multiparametric, quantitative and high-throughput assay to quantify the influence of target size on phagocytic uptake

2018 ◽  
Author(s):  
Lorraine Montel ◽  
Léa Pinon ◽  
Jacques Fattaccioli
Keyword(s):  
Meta Analysis ◽  
Cell Types ◽  
Automated Image Analysis ◽  
Cellular Targets ◽  
Intensity Parameters ◽  
A Cell ◽  
High Throughput Assay ◽  
The Relationship ◽  
Phagocytic Uptake

Phagocytosis by macrophages represents a fundamental process essential for both immunity and tissue homeostasis. It consists in the uptake of pathogenic or cellular targets larger than 0.5μm. For the biggest particles, the phagocytic process involves a massive reorganization of membrane and actin cytoskeleton as well as an important intracellular deformation, all in a matter of minutes. The study of the role of the size of objects in their phagocytosis has lead to contradictory results in the last decades. We designed a method using confocal microscopy, automated image analysis and databases for fast quantitative analysis of phagocytosis assays. It yields comprehensive data on the cells and targets geometric and fluorescence intensity parameters, automatically discriminates internalized from external targets, and stores the relationship between a cell and the targets it has engulfed. We used two types of targets, solid polystyrene beads and liquid lipid droplets, to investigate the influence of size on the phagocytic uptake of macrophages. The method made it possible, not only to perform phagocytic assays with functionalized droplets and beads of different sizes, but to use polydisperse particles to further our understanding of the role of size in phagocytosis. The use of monodisperse and polydisperse objects shows that while smaller monodisperse objects are internalized in greater numbers, objects of different sizes presented simultaneously are internalized without preferred size. Throughout results, the total surface engulfed by the cell appeared to be the main factor limiting the uptake of particles, regardless of their nature or size. A meta-analysis of the literature reveals that this dependence in surface is consistently conserved throughout cell types, nature of targets or activated receptors.

scholarly journals Mechanistic paradigms of cell death - revisited

2021 ◽  
Vol 42 (4) ◽  
pp. 903-917
Author(s):  
S.V.S. Rana ◽  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Human Health Risk ◽  
Cell Types ◽  
Enzymatic Antioxidants ◽  
Cellular Targets ◽  
A Cell ◽  
The Impact ◽  
Made In

Present review is the description of a journey that originates from Virchows' cell theory and terminates with the role of molecular switches in cell death recently proposed by Orrenius. Landmark discoveries made, in between, to characterize regulated as well as accidental cell death have also been documented. It embraces the studies that were made in early nineties to understand cellular homeostasis in health and disease. Furthermore, the effects of foreign chemicals on different cell types witnessed in late nineties have been classified into necrosis, apoptosis, autophagy etc. Since it is important to know how a cell dies, studies made in our own and other laboratories on the role of reactive oxygen species, oxidative stress, intracellular Ca2+ homeostasis, redox imbalance, mitochondrial and ER stress in cell death have also been reviewed. Possibility of a cross talk amongst these mechanisms has also been examined. It discusses the impact of wonder molecules like CYP450, GSH, metallothionein and melatonin together with enzymatic and non-enzymatic antioxidants on cell death. Understanding the cellular targets and molecular mechanisms activated by a variety of environmental xenobiotics is fundamental for human health risk assessment. It is expected that the contents of this article will answer the fundamental question- why and how cells die.

scholarly journals Role of Thyroid Hormone Receptor Subtypes α and β on Gene Expression in the Cerebral Cortex and Striatum of Postnatal Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (5) ◽  
pp. 1940-1947 ◽  
Author(s):  
Pilar Gil-Ibañez ◽  
Beatriz Morte ◽  
Juan Bernal
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Thyroid Hormone Receptor ◽  
Intrinsic Activity ◽  
Receptor Subtypes ◽  
Rt Pcr ◽  
Control Of Gene Expression ◽  
Total Absence ◽  
And Function

Abstract The effects of thyroid hormones (THs) on brain development and function are largely mediated by the control of gene expression. This is achieved by the binding of the genomically active T3 to transcriptionally active nuclear TH receptors (TRs). T3 and the TRs can either induce or repress transcription. In hypothyroidism, the reduction of T3 lowers the expression of a set of genes, the positively regulated genes, and increases the expression of negatively regulated genes. Two mechanisms may account for the effect of hypothyroidism on genes regulated directly by T3: first, the loss of T3 signaling and TR transactivation, and second, an intrinsic activity of the unliganded TRs directly responsible for repression of positive genes and enhancement of negative genes. To analyze the contribution of the TR subtypes α and β, we have measured by RT-PCR the expression of a set of positive and negative genes in the cerebral cortex and the striatum of TR-knockout male and female mice. The results indicate that TRα1 exerts a predominant but not exclusive role in the regulation of positive and negative genes. However, a fraction of the genes analyzed are not or only mildly affected by the total absence of TRs. Furthermore, hypothyroidism has a mild effect on these genes in the absence of TRα1, in agreement with a role of unliganded TRα1 in the effects of hypothyroidism.

Role of Intermediate Progenitor Cells in Cerebral Cortex Development

2007 ◽  
Vol 30 (1-3) ◽  
pp. 24-32 ◽  
Author(s):  
Adria Pontious ◽  
Tom Kowalczyk ◽  
Chris Englund ◽  
Robert F. Hevner
Keyword(s):  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Cerebral Cortex Development
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