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https://www.readbyqxmd.com/read/29760194/differential-roles-of-lt%C3%AE-r-in-endothelial-cell-subsets-for-lymph-node-organogenesis-and-maturation
#1
Zhongnan Wang, Qian Chai, Mingzhao Zhu
Cellular cross-talk mediated by lymphotoxin αβ-lymphotoxin β receptor (LTβR) signaling plays a critical role in lymph node (LN) development. Although the major role of LTβR signaling has long been considered to occur in mesenchymal lymphoid tissue organizer cells, a recent study using a VE-cadherincre Ltbrfl/fl mouse model suggested that endothelial LTβR signaling contributes to the formation of LNs. However, the detailed roles of LTβR in different endothelial cells (ECs) in LN development remain unknown...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29760176/postnatal-ablation-of-synaptic-retinoic-acid-signaling-impairs-cortical-information-processing-and-sensory-discrimination-in-mice
#2
Esther Park, Michelle Tjia, Yi Zuo, Lu Chen
Retinoic acid (RA) and its receptors (RARs) are well-established essential transcriptional regulators during embryonic development. Recent findings in cultured neurons identified an independent and critical post-transcriptional role of RA and RARα in the homeostatic regulation of excitatory and inhibitory synaptic transmission in mature neurons. However, the functional relevance of synaptic RA signaling in vivo has not been established. Here, using somatosensory cortex as a model system and the RARα conditional knockout mouse as a tool, we applied multiple genetic manipulations to delete RARα postnatally in specific populations of cortical neurons, and asked whether synaptic RA signaling observed in cultured neurons is involved in cortical information processing in vivo Indeed, conditional ablation of RARα in mice via a CaMKIIα-Cre or a layer 5-Cre driver line or via somatosensory cortex-specific viral expression of Cre-recombinase impaired whisker-dependent texture discrimination, suggesting a critical requirement of RARα expression in L5 pyramidal neurons of somatosensory cortex for normal tactile sensory processing...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29752955/skeletal-muscle-specific-sidt2-knockout-in-mice-induced-muscular-dystrophy-like-phenotype
#3
Huan Liu, Wenjun Jiang, Xueru Chen, Guoying Chang, Lei Zhao, Xihua Li, Huiwen Zhang
BACKGROUND: Sidt2 is an integral lysosomal membrane protein. Previously, we generated a Sidt2 global knockout mouse and found impaired insulin secretion, along with skeletal muscle pathology. METHODS: A mouse model with a muscle-specific knockout of the Sidt2 gene (Sidt2f/f Cre) had been generated, to which extensive morphologic study as well as functional study was applied to investigate the direct role of Sidt2 on skeletal muscle tissue in vivo. Secondly, the autophagy-lysosomal pathway was examined by Western blot and immunostaining...
May 9, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29750959/a-btb-zf-protein-znf131-is-required-for-early-b-cell-development
#4
Tomohiro Iguchi, Emako Miyauchi, Sumiko Watanabe, Hisao Masai, Shoichiro Miyatake
Members of the BTB-ZF transcription factor family play important roles in lymphocyte development. During T cell development, ZNF131, a BTB-ZF protein, is critical for the double-negative (DN) to double-positive (DP) transition and is also involved in cell proliferation. Here, we report that knockout of Znf131 at the pre-pro-B cell stage in mb1-Cre knock-in mouse resulted in defect of pro-B to pre-B cell transition. ZNF131 was shown to be required for efficient pro-B cell proliferation as well as for immunoglobulin heavy chain gene rearrangement that occur in the proliferating pro-B cells...
May 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29739868/the-dorsal-wave-of-neocortical-oligodendrogenesis-begins-embryonically-and-requires-multiple-sources-of-sonic-hedgehog
#5
Caitlin C Winkler, Odessa R Yabut, Santiago P Fregoso, Hector G Gomez, Brett E Dwyer, Samuel J Pleasure, Santos J Franco
Neural progenitor cells in the developing dorsal forebrain give rise to excitatory neurons, astrocytes and oligodendrocytes for the neocortex. Compared to neurons and astrocytes, less is known about the molecular mechanisms that instruct dorsal forebrain progenitors to an oligodendrocyte fate. In this study, we show that Sonic hedgehog (Shh) signaling is required in dorsal progenitors for their late embryonic transition to oligodendrogenesis. Using genetic lineage-tracing in mice of both sexes, we demonstrate that the majority of oligodendrocytes in the embryonic neocortex derive from Emx1+ dorsal forebrain progenitors...
May 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29735531/smad4-deficiency-impairs-chondrocyte-hypertrophy-via-the-runx2-transcription-factor-in-mouse-skeletal-development
#6
Jianyun Yan, Jun Li, Jun Hu, Lu Zhang, Chengguo Wei, Nishat Sultana, Xiaoqiang Cai, Weijia Zhang, Chen-Leng Cai
Chondrocyte hypertrophy is the terminal step in chondrocyte differentiation and is crucial for endochondral bone formation. How signaling pathways regulate chondrocyte hypertrophic differentiation remains incompletely understood. In this study, using a Tbx18:Cre (Tbx18Cre/+) gene-deletion approach, we selectively deleted the gene for the signaling protein SMAD family member 4 (Smad4f/f) in the limbs of mice. We found that the Smad4-deficient mice develop a prominent shortened limb, with decreased expression of chondrocyte differentiation markers, including Col2a1 and Acan, in the humerus at mid-to-late gestation...
May 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29733854/structural-insights-into-the-crtc2-creb-complex-assembly-on-cre
#7
Yihui Song, Liting Zhai, Jonathan Valencia Swain, Yaqiong Chen, Pengfei Wang, Li Chen, Yi Liu, Song Xiang
The cAMP Response Element (CRE) Binding protein (CREB) is central in the transcription regulation by cAMP, and the CREB-Regulated Transcriptional Coactivators (CRTCs) play critical roles in CREB-mediated transcription activation. Upon stimulation, CRTCs translocate into the nucleus and complex with CREB on CRE promoters to activate target gene transcription. Their physiological importance is underscored by their function in energy balance, long-term memory, longevity and other processes. The CREB Binding Domain (CBD) on CRTCs has been mapped, which interacts with the CREB basic leucine zipper (bZip) domain that also mediates interaction with CRE-containing DNA...
May 4, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29732603/sox2-conditional-mutation-in-mouse-causes-ataxic-symptoms-cerebellar-vermis-hypoplasia-and-postnatal-defects-of-bergmann-glia
#8
Valentina Cerrato, Sara Mercurio, Ketty Leto, Elisa Fucà, Eriola Hoxha, Sara Bottes, Miriam Pagin, Marco Milanese, Chew-Yee Ngan, Giulia Concina, Sergio Ottolenghi, Chia-Lin Wei, Giambattista Bonanno, Giulio Pavesi, Filippo Tempia, Annalisa Buffo, Silvia K Nicolis
Sox2 is a transcription factor active in the nervous system, within different cell types, ranging from radial glia neural stem cells to a few specific types of differentiated glia and neurons. Mutations in the human SOX2 transcription factor gene cause various central nervous system (CNS) abnormalities, involving hippocampus and eye defects, as well as ataxia. Conditional Sox2 mutation in mouse, with different Cre transgenes, previously recapitulated different essential features of the disease, such as hippocampus and eye defects...
May 6, 2018: Glia
https://www.readbyqxmd.com/read/29727702/prmt1-regulates-craniofacial-bone-formation-upstream-of-msx1
#9
Yongchao Gou, Jingyuan Li, Jian Wu, Rahul Gupta, Ihnbae Cho, Thach-Vu Ho, Yang Chai, Amy Merrill, Jun Wang, Jian Xu
Protein arginine methylation has been recently identified as an important form of post-translational modification (PTM). It is carried out by the protein arginine methyltransferase (PRMT) family of enzymes, which in mammals consists of nine members. Among them, PRMT1 is the major arginine methyltransferase and participates in transcription, signal transduction, development and cancer. The function of PRMT1 in craniofacial development remains unclear. We generated Wnt1-Cre;Prmt1fl/fl mice with cranial neural crest (CNC)-specific deletion of Prmt1 and compared CNC-derived craniofacial bones from newborn control and Wnt1-Cre;Prmt1fl/fl mice...
May 1, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/29720668/central-role-of-the-proximal-tubular-%C3%AE-klotho-fgf-receptor-complex-in-fgf23-regulated-phosphate-and-vitamin-d-metabolism
#10
Ai Takeshita, Kazuki Kawakami, Kenryo Furushima, Masayasu Miyajima, Kazushige Sakaguchi
Fibroblast growth factor 23 (FGF23) plays critical roles in phosphate handling and vitamin D metabolism in the kidney. However, the effector cells of FGF23 in the kidney remain unclear. αKlotho, a putative enzyme possessing β-glucuronidase activity and also a permissive co-receptor for FGF23 to bind to FGF receptors (FGFRs), is expressed most abundantly in distal convoluted tubules, whereas it is expressed modestly in proximal tubules. Key molecular players of phosphate homeostasis and vitamin D-metabolizing enzymes are known to localize in proximal tubules...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29718413/understanding-molecular-evolution-and-development-of-the-organ-of-corti-can-provide-clues-for-hearing-restoration
#11
Israt Jahan, Karen L Elliott, Bernd Fritzsch
The mammalian hearing organ is a stereotyped cellular assembly with orderly innervation: two types of spiral ganglion neurons (SGNs) innervate two types of differentially distributed hair cells (HCs). HCs and SGNs evolved from single neurosensory cells through gene multiplication and diversification. Independent regulation of HCs and neuronal differentiation through expression of basic Helix-loop-Helix transcription factors (bHLH TFs: Atoh1, Neurog1, Neurod1) led to the evolution of vestibular HC assembly and their unique type of innervation...
April 26, 2018: Integrative and Comparative Biology
https://www.readbyqxmd.com/read/29704006/intracellular-glycolysis-in-brown-adipose-tissue-is-essential-for-optogenetically-induced-nonshivering-thermogenesis-in-mice
#12
Jae Hoon Jeong, Ji Suk Chang, Young-Hwan Jo
Release of fatty acids from lipid droplets upon activation of the sympathetic nervous system (SNS) is a key step in nonshivering thermogenesis in brown adipose tissue (BAT). However, intracellular lipolysis appears not to be critical for cold-induced thermogenesis. As activation of the SNS increases glucose uptake, we studied whether intracellular glycolysis plays a role in BAT thermogenesis. To stimulate BAT-innervating sympathetic nerves in vivo, we expressed channelrhodopsin-2 (ChR2) in catecholaminergic fibers by crossbreeding tyrosine hydroxylase-Cre mice with floxed-stop ChR2 mice...
April 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29701891/cell-lineage-tracing-in-zebrafish-embryos-with-an-expanded-genetic-code
#13
Wes Brown, Jihe Liu, Michael Tsang, Alexander Deiters
Cell lineage tracing is used to study embryo development, stem cell differentiation, and to document tumor cell heterogeneity. Cre recombinase-mediated cell labelling is the preferred approach; however, its utility is restricted by when and where DNA recombination takes place. We generated a photoactivatable Cre recombinase by replacing a critical residue in its active site with a photocaged lysine derivative through genetic code expansion in zebrafish embryos. This allows for high spatiotemporal control of DNA recombination using 405 nm light...
April 27, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29684311/tfam-is-required-for-maturation-of-the-fetal-and-adult-intestinal-epithelium
#14
Manasa Srivillibhuthur, Bailey N Warder, Natalie H Toke, Pooja P Shah, Qiang Feng, Nan Gao, Edward M Bonder, Michael P Verzi
During development, the embryo transitions from a metabolism favoring glycolysis to a metabolism favoring mitochondrial respiration. How metabolic shifts regulate developmental processes, or how developmental processes regulate metabolic shifts, remains unclear. To test the requirement of mitochondrial function in developing endoderm-derived tissues, we genetically inactivated the mitochondrial transcription factor, Tfam, using the Shh-Cre driver. Tfam mutants did not survive postnatally, exhibiting defects in lung development...
April 20, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29665845/deletion-of-hp1%C3%AE-in-cardiac-myocytes-affects-h4k20me3-levels-but-does-not-impact-cardiac-growth
#15
Kyohei Oyama, Danny El-Nachef, Chen Fang, Hidemi Kajimoto, Jeremy P Brown, Prim B Singh, W Robb MacLellan
BACKGROUND: Heterochromatin, which is formed when tri-methyl lysine 9 of histone H3 (H3K9me3) is bound by heterochromatin 1 proteins (HP1s), plays an important role in differentiation and senescence by silencing cell cycle genes. Cardiac myocytes (CMs) accumulate heterochromatin during differentiation and demethylation of H3K9me3 inhibits cell cycle gene silencing and cell cycle exit in CMs; however, it is unclear if this process is mediated by HP1s. In this study, we created a conditional CM-specific HP1 gamma (HP1γ) knockout (KO) mouse model and tested whether HP1γ is required for cell cycle gene silencing and cardiac growth...
April 17, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29657865/stress-adaptive-responses-associated-with-high-level-carbapenem-resistance-in-kpc-producing-klebsiella-pneumoniae
#16
Sheila Adams-Sapper, Adam Gayoso, Lee W Riley
Carbapenem-resistant Enterobacteriaceae (CRE) organisms have emerged to become a major global public health threat among antimicrobial resistant bacterial human pathogens. Little is known about how CREs emerge. One characteristic phenotype of CREs is heteroresistance, which is clinically associated with treatment failure in patients given a carbapenem. Through in vitro whole-transcriptome analysis we tracked gene expression over time in two different strains (BR7, BR21) of heteroresistant KPC-producing Klebsiella pneumoniae, first exposed to a bactericidal concentration of imipenem followed by growth in drug-free medium...
2018: Journal of Pathogens
https://www.readbyqxmd.com/read/29644115/shp2-regulates-skeletal-cell-fate-by-modifying-sox9-expression-and-transcriptional-activity
#17
Chunlin Zuo, Lijun Wang, Raghavendra M Kamalesh, Margot E Bowen, Douglas C Moore, Mark S Dooner, Anthony M Reginato, Qian Wu, Christoph Schorl, Yueming Song, Matthew L Warman, Benjamin G Neel, Michael G Ehrlich, Wentian Yang
Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor (OCP), and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2 (encoded by Ptpn11 ) affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using "Cre-loxP"-mediated gene excision. SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts...
2018: Bone Research
https://www.readbyqxmd.com/read/29618523/tuning-t-cell-signaling-sensitivity-alters-the-behavior-of-cd4-t-cells-during-an-immune-response
#18
Ashley A Viehmann Milam, Juliet M Bartleson, David L Donermeyer, Stephen Horvath, Vivek Durai, Saravanan Raju, Haiyang Yu, Veronika Redmann, Bernd Zinselmeyer, J Michael White, Kenneth M Murphy, Paul M Allen
Intricate processes in the thymus and periphery help curb the development and activation of autoreactive T cells. The subtle signals that govern these processes are an area of great interest, but tuning TCR sensitivity for the purpose of affecting T cell behavior remains technically challenging. Previously, our laboratory described the derivation of two TCR-transgenic CD4 T cell mouse lines, LLO56 and LLO118, which recognize the same cognate Listeria epitope with the same affinity. Despite the similarity of the two TCRs, LLO56 cells respond poorly in a primary infection whereas LLO118 cells respond robustly...
April 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29616043/lineage-specific-analysis-of-syk-function-in-autoantibody-induced-arthritis
#19
Tamás Németh, Krisztina Futosi, Kata Szilveszter, Olivér Vilinovszki, Levente Kiss-Pápai, Attila Mócsai
Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contribute to inflammation and tissue damage in this model. We have previously shown that the Syk tyrosine kinase is critically involved in the development in K/BxN serum-transfer arthritis and bone marrow chimeric experiments indicated that Syk is likely involved in one or more hematopoietic lineages during the disease course...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29615467/late-neuroprogenitors-contribute-to-normal-retinal-vascular-development-in-a-hif2a-dependent-manner
#20
Enrico Cristante, Sidath E Liyanage, Robert D Sampson, Aikaterini Kalargyrou, Giulia De Rossi, Matteo Rizzi, Justin Hoke, Joana Ribeiro, Ryea N Maswood, Yanai Duran, Takaaki Matsuki, Nozie Aghaizu, Ulrich F Luhmann, Alexander J Smith, Robin R Ali, James W B Bainbridge
In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of their critical relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a ( Hif2a )...
April 3, 2018: Development
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