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https://www.readbyqxmd.com/read/28065741/essential-roles-for-cdx-in-murine-primitive-hematopoiesis
#1
Travis Brooke-Bisschop, Joanne G A Savory, Tanya Foley, Randy Ringuette, David Lohnes
The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis...
January 5, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28062693/pu-1-regulates-ig-light-chain-transcription-and-rearrangement-in-pre-b-cells-during-b-cell-development
#2
Carolina R Batista, Stephen K H Li, Li S Xu, Lauren A Solomon, Rodney P DeKoter
B cell development and Ig rearrangement are governed by cell type- and developmental stage-specific transcription factors. PU.1 and Spi-B are E26-transformation-specific transcription factors that are critical for B cell differentiation. To determine whether PU.1 and Spi-B are required for B cell development in the bone marrow, Spi1 (encoding PU.1) was conditionally deleted in B cells by Cre recombinase under control of the Mb1 gene in Spib (encoding Spi-B)-deficient mice. Combined deletion of Spi1 and Spib resulted in a lack of mature B cells in the spleen and a block in B cell development in the bone marrow at the small pre-B cell stage...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28057770/neuroendocrine-integration-of-nutritional-signals-on-reproduction
#3
Maggie Corr Evans, Greg Anderson
Reproductive function in mammals is energetically costly and therefore tightly regulated by nutritional status. To enable this integration of metabolic and reproductive function, information regarding peripheral nutritional status must be relayed centrally to the gonadotropin-releasing hormone (GnRH) neurons that drive reproductive function. The metabolically relevant hormones leptin, insulin and ghrelin have been identified as key mediators of this 'metabolic control of fertility'. However, the neural circuitry through which they act to exert their control over GnRH drive remains incompletely understood...
January 5, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28049832/forkhead-box-a2-foxa2-is-essential-for-uterine-function-and-fertility
#4
Andrew M Kelleher, Wang Peng, James K Pru, Cindy A Pru, Francesco J DeMayo, Thomas E Spencer
Establishment of pregnancy is a critical event, and failure of embryo implantation and stromal decidualization in the uterus contribute to significant numbers of pregnancy losses in women. Glands of the uterus are essential for establishment of pregnancy in mice and likely in humans. Forkhead box a2 (FOXA2) is a transcription factor expressed specifically in the glands of the uterus and is a critical regulator of postnatal uterine gland differentiation in mice. In this study, we conditionally deleted FOXA2 in the adult mouse uterus using the lactotransferrin Cre (Ltf-Cre) model and in the neonatal mouse uterus using the progesterone receptor Cre (Pgr-Cre) model...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28039555/disruption-of-non-anchored-cell-wall-protein-ncw-1-promotes-cellulase-production-by-increasing-cellobiose-uptake-in-neurospora-crassa
#5
Liangcai Lin, Yong Chen, Jingen Li, Shanshan Wang, Wenliang Sun, Chaoguang Tian
OBJECTIVES: To elucidate the mechanism of cellulase signal transduction in filamentous fungi including the components of the cellulase induction pathway. RESULTS: Neurospora crassa ncw-1 encodes a non-anchored cell wall protein. The absence of ncw-1 increased cellulase gene expression and this is not due to relieving carbon catabolite repression mediated by the cre-1 pathway. A mutant lacking genes encoding both three major β-glucosidase enzymes and NCW-1 (Δ3βGΔncw-1) was constructed...
December 30, 2016: Biotechnology Letters
https://www.readbyqxmd.com/read/28039362/defining-the-temporal-course-of-murine-neurofibromatosis-1-optic-gliomagenesis-reveals-a-therapeutic-window-to-attenuate-retinal-dysfunction
#6
Joseph A Toonen, Yu Ma, David H Gutmann
BACKGROUND: Optic gliomas arising in the neurofibromatosis type 1 (NF1) cancer predisposition syndrome cause reduced visual acuity in 30%-50% of affected children. Since human specimens are rare, genetically engineered mouse (GEM) models have been successfully employed for preclinical therapeutic discovery and validation. However, the sequence of cellular and molecular events that culminate in retinal dysfunction and vision loss has not been fully defined relevant to potential neuroprotective treatment strategies...
December 29, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28039299/hyperactivation-of-the-nlrp3-inflammasome-in-myeloid-cells-leads-to-severe-organ-damage-in-experimental-lupus
#7
Ailing Lu, Hua Li, Junling Niu, Shuxian Wu, Guang Xue, Xiaomin Yao, Qiuhong Guo, Nianhong Wan, Paride Abliz, Guiwen Yang, Liguo An, Guangxun Meng
Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model...
December 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28003412/dicer-maintains-the-identity-and-function-of-proprioceptive-sensory-neurons
#8
Sean Michael O'Toole, Monica M Ferrer, Jennifer Mekonnen, Haihan Zhang, Yasuyuki Shima, David R Ladle, Sacha B Nelson
Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell and Heintz 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris and Hobert 2014). Post-transcriptional regulation also plays an important role in neuronal differentiation (Bian and Sun 2011), but its role in maintaining cell identity is less established. To better understand how post-transcriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well established properties that distinguish them from other neurons in the ganglion...
December 21, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27998825/hematopoietic-arginase-1-deficiency-results-in-decreased-leukocytosis-and-increased-foam-cell-formation-but-does-not-affect-atherosclerosis
#9
Baoyan Ren, Erik Van Kampen, Theo J C Van Berkel, Sheena M Cruickshank, Miranda Van Eck
BACKGROUND AND AIMS: Arginase1 (Arg1), an M2 macrophage marker, plays a critical role in a number of immunological functions in macrophages, which are the main cell type facilitating atherosclerotic lesion development. Arg1 uses the substrate l-arginine to create l-ornithine, a precursor molecule required for collagen formation and vascular smooth muscle cell differentiation. By reducing l-arginine availability, Arg1 limits the production of nitric oxide (NO), a pro-atherogenic factor in macrophages...
November 16, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27940158/inactivation-of-maternal-hif-1%C3%AE-at-mid-pregnancy-causes-placental-defects-and-deficits-in-oxygen-delivery-to-the-fetal-organs-under-hypoxic-stress
#10
Doreswamy Kenchegowda, Bryony Natale, Maria A Lemus, David R Natale, Steven A Fisher
A critical transition occurs near mid-gestation of mammalian pregnancy. Prior to this transition, low concentrations of oxygen (hypoxia) signaling through Hypoxia Inducible Factor (HIF) functions as a morphogen for the placenta and fetal organs. Subsequently, functional coupling of the placenta and fetal cardiovascular system for oxygen (O2) transport is required to support the continued growth and development of the fetus. Here we tested the hypothesis that Hif-1α is required in maternal cells for placental morphogenesis and function...
December 9, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27939685/regionally-restricted-hox-function-in-adult-bone-marrow-multipotent-mesenchymal-stem-stromal-cells
#11
Danielle R Rux, Jane Y Song, Ilea T Swinehart, Kyriel M Pineault, Aleesa J Schlientz, Kelsey G Trulik, Steve A Goldstein, Ken M Kozloff, Daniel Lucas, Deneen M Wellik
Posterior Hox genes (Hox9-13) are critical for patterning the limb skeleton along the proximodistal axis during embryonic development. Here we show that Hox11 paralogous genes, which developmentally pattern the zeugopod (radius/ulna and tibia/fibula), remain regionally expressed in the adult skeleton. Using Hoxa11EGFP reporter mice, we demonstrate expression exclusively in multipotent mesenchymal stromal cells (MSCs) in the bone marrow of the adult zeugopod. Hox-positive cells express PDGFRα and CD51, are marked by LepR-Cre, and exhibit colony-forming unit fibroblast activity and tri-lineage differentiation in vitro...
December 19, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27939396/a-role-for-peroxisome-proliferator-activated-receptor-gamma-coactivator-1%C3%AE-in-nucleus-accumbens-neuron-subtypes-in-cocaine-action
#12
Ramesh Chandra, Michel Engeln, T Chase Francis, Prasad Konkalmatt, Dipal Patel, Mary Kay Lobo
BACKGROUND: Molecules critically involved in cocaine behavioral plasticity are known to regulate and interact with peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). In addition, the PGC-1α promoter has binding sites for early growth response 3 (Egr3), which plays a dynamic role in cocaine action in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 (D1-MSN) versus D2 (D2-MSN). However, the role of PGC-1α in NAc in cocaine action is unknown...
October 28, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27922639/mesolimbic-leptin-signaling-negatively-regulates-cocaine-conditioned-reward
#13
M Shen, C Jiang, P Liu, F Wang, L Ma
The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27912078/mouse-double-minute-2-homolog-actively-suppresses-p53-activity-in-oocytes-during-mouse-folliculogenesis
#14
Chen-Xi Zhang, Qin Zhang, Yin-Yin Xie, Xue-Yan He, Cong Xiang, Xiao-Shuang Hou, Ying Zhou, Lai Chen, Guo-Xin Zhang, Geng Liu
The p53 signaling network is indispensible in cellular stress responses and tumor suppression. Negative regulations of p53 by mouse double minute 2 and 4 homologs (MDM2) and (MDM4) are an integrated component of the network and have been implicated in regulating the stress responses and the maintenance of normal development and homeostasis of multiple somatic cell lineages. However, the regulatory role of MDM2 on p53 and stress responses in female germ cells remains undetermined. Here, we used the Cre-loxP system to delete Mdm2 in oocytes at different stages of folliculogenesis in mice...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27911782/egfr-signaling-is-critical-for-maintaining-the-superficial-layer-of-articular-cartilage-and-preventing-osteoarthritis-initiation
#15
Haoruo Jia, Xiaoyuan Ma, Wei Tong, Basak Doyran, Zeyang Sun, Luqiang Wang, Xianrong Zhang, Yilu Zhou, Farid Badar, Abhishek Chandra, X Lucas Lu, Yang Xia, Lin Han, Motomi Enomoto-Iwamoto, Ling Qin
Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox)...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909303/conditional-knockout-of-n-wasp-in-mouse-fibroblast-caused-keratinocyte-hyper-proliferation-and-enhanced-wound-closure
#16
Neeraj Jain, Pazhanichamy Kalailingam, Kai Wei Tan, Hui Bing Tan, Ming Keat Sng, Jeremy Soon Kiat Chan, Nguan Soon Tan, Thirumaran Thanabalu
Neural-Wiskott Aldrich Syndrome Protein (N-WASP) is expressed ubiquitously, regulates actin polymerization and is essential during mouse development. We have previously shown that N-WASP is critical for cell-ECM adhesion in fibroblasts. To characterize the role of N-WASP in fibroblast for skin development, we generated a conditional knockout mouse model in which fibroblast N-WASP was ablated using the Cre recombinase driven by Fibroblast Specific Protein promoter (Fsp-Cre). N-WASP(FKO) (N-WASP(fl/fl); Fsp-cre) were born following Mendelian genetics, survived without any visible abnormalities for more than 1 year and were sexually reproductive, suggesting that expression of N-WASP in fibroblast is not critical for survival under laboratory conditions...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907249/grainyhead-like-3-grhl3-deficiency-in-brain-leads-to-altered-locomotor-activity-and-decreased-anxiety-like-behaviours-in-aged-mice
#17
Sebastian Dworkin, Alana Auden, Darren D Partridge, Maria Daglas, Robert L Medcalf, Theo Mantamadiotis, Smitha R Georgy, Charbel Darido, Stephen M Jane, Stephen B Ting
The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here we show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviours...
December 1, 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#18
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27896618/loss-of-liver-kinase-b1-causes-planar-polarity-defects-in-cochlear-hair-cells-in-mice
#19
Yuqin Men, Aizhen Zhang, Liwen Zhang, Yecheng Jin, Zhishuo Wang, Jing Zhao, Xiaolin Yu, Jian Zhang, Jiangang Gao
The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a serine/threonine kinase. LKB1 plays crucial roles in cell differentiation, proliferation, and polarity. In this study, LKB1 conditional knockout mice (LKB1(Pax2) CKO mice) were generated using Pax2-Cre mice to investigate the function of LKB1 in inner ear hair cells during early embryonic period. LKB1(Pax2) CKO mice died perinatally. Immunofluorescence and scanning electron microscopy revealed that stereociliary bundles in LKB1(Pax2) CKO mice were clustered and misoriented, respectively...
November 28, 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27881487/osteogenesis-requires-fak-dependent-collagen-synthesis-by-fibroblasts-and-osteoblasts
#20
Dhaarmini Rajshankar, Yongqiang Wang, Christopher A McCulloch
Focal adhesion kinase (FAK) is critical in adhesion-dependent signaling, but its role in osteogenesis in vivo is ill defined. We deleted Fak in fibroblasts and osteoblasts in Floxed-Fak mice bred with those expressing Cre-recombinase driven by 3.6 kb α1(I)-collagen promoter. Compared with wild-type (WT), conditional FAK-knockout (CFKO) mice were shorter (2-fold; P < 0.0001) and had crooked, shorter tails (50%; P < 0.0001). Microcomputed tomography analysis showed reduced bone volume (4-fold in tails; P < 0...
November 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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