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https://www.readbyqxmd.com/read/28441416/ethanol-itself-is-a-holoprosencephaly-inducing-teratogen
#1
Mingi Hong, Robert S Krauss
Ethanol is a teratogen, inducing a variety of structural defects in developing humans and animals that are exposed in utero. Mechanisms of ethanol teratogenicity in specific defects are not well understood. Oxidative metabolism of ethanol by alcohol dehydrogenase or cytochrome P450 2E1 has been implicated in some of ethanol's teratogenic effects, either via production of acetaldehyde or competitive inhibition of retinoic acid synthesis. Generalized oxidative stress in response to ethanol may also play a role in its teratogenicity...
2017: PloS One
https://www.readbyqxmd.com/read/28438991/differentiation-of-v2a-interneurons-from-human-pluripotent-stem-cells
#2
Jessica C Butts, Dylan A McCreedy, Jorge Alexis Martinez-Vargas, Frederico N Mendoza-Camacho, Tracy A Hookway, Casey A Gifford, Praveen Taneja, Linda Noble-Haeusslein, Todd C McDevitt
The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10(+) V2a interneurons from human pluripotent stem cells (hPSCs)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28432216/embryonic-cholecystitis-and-defective-gallbladder-contraction-in-the-sox17-haploinsufficient-model-of-biliary-atresia
#3
Hiroki Higashiyama, Aisa Ozawa, Hiroyuki Sumitomo, Mami Uemura, Ko Fujino, Hitomi Igarashi, Kenya Imaimatsu, Naoki Tsunekawa, Yoshikazu Hirate, Masamichi Kurohmaru, Yukio Saijoh, Masami Kanai-Azuma, Yoshiakira Kanai
The gallbladder excretes cytotoxic bile acids to the duodenum through the cystic duct and common bile duct system. Sox17 haploinsufficiency causes the biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos. However, the molecular and cellular mechanisms in the Sox17-haploinsufficient gallbladder and liver in the etiology of biliary atresia remain unclear. In this study, transcriptomic analyses revealed the early onset of cholecystitis in the Sox17(+/-) embryos, together with the appearance of ectopic cystic duct-like epithelia in their gallbladders...
April 21, 2017: Development
https://www.readbyqxmd.com/read/28427488/nr2e1-downregulation-is-involved-in-excess-retinoic-acid-induced-developmental-abnormality-in-the-mouse-brain
#4
Juan Yu, Qian Guo, Jian Bing Mu, Ting Zhang, Ren Ke Li, Jun Xie
OBJECTIVE: This study aimed to investigate the expression pattern and function of Nuclear receptor subfamily 2 group E member 1 (Nr2e1) in retinoic acid (RA)-induced brain abnormality. METHODS: The mouse model of brain abnormality was established by administering 28 mg/kg RA, and neural stem cells (NSCs) were isolated from the mouse embryo and cultured in vitro. Nr2e1 expression was detected by whole mount in situ hybridization, RT-PCR, and Western blotting. Nr2e1 function was determined by transducing Nr2e1 shRNA into NSCs, and the effect on the sonic hedgehog (Shh) signaling pathway was assessed in the cells...
March 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28416808/ptchd1-deficiency-induces-excitatory-synaptic-and-cognitive-dysfunctions-in-mouse
#5
D C Ung, G Iacono, H Méziane, E Blanchard, M-A Papon, M Selten, J-R van Rhijn, R Montjean, J Rucci, S Martin, A Fleet, M-C Birling, S Marouillat, R Roepman, M Selloum, A Lux, R-A Thépault, P Hamel, K Mittal, J B Vincent, O Dorseuil, H G Stunnenberg, P Billuart, N Nadif Kasri, Y Hérault, F Laumonnier
Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD...
April 18, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28415132/genetic-alterations-in-mesiodens-as-revealed-by-targeted-ngs-and-gene-co-occurrence-network-analysis
#6
Young Youn Kim, Jihye Hwang, Hye-Sung Kim, Hee Jun Kwon, Sanguk Kim, Ji Hyun Lee, Jae Hoon Lee
OBJECTIVE: Mesiodens is the most common type of supernumerary tooth which includes a population prevalence of 0.15-1.9%. Alongside evidence that the condition is heritable, mutations in single genes have been reported in few human supernumerary tooth cases. Gene sequencing methods in tradition way are time-consuming and labor-intensive, whereas next generation sequencing and bioinformatics are cost-effective for large samples and target sizes. MATERIALS AND METHODS: We describe the application of a targeted next generation sequencing (NGS) and bioinformatics approach to samples from 17 mesiodens patients...
April 17, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28412462/spop-regulates-gli3-activity-and-shh-signaling-in-dorsoventral-patterning-of-the-mouse-spinal-cord
#7
Hongchen Cai, Aimin Liu
Sonic Hedgehog (Shh) signaling regulates the patterning of ventral spinal cord through the effector Gli family of transcription factors. Previous in vitro studies showed that an E3 ubiquitin ligase containing Speckle-type POZ protein (Spop) targets Gli2 and Gli3 for ubiquitination and degradation, but the role of Spop in Shh signaling and mammalian spinal cord patterning remains unknown. Here, we show that loss of Spop does not alter spinal cord patterning, but it suppresses the loss of floor plate and V3 interneuron phenotype of Gli2 mutants, suggesting a negative role of Spop in Gli3 activator activity, Shh signaling and the specification of ventral cell fates in the spinal cord...
April 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28409313/extracellular-regulation-of-the-mitotic-spindle-and-fate-determinants-driving-asymmetric-cell-division
#8
Prestina Smith, Mark Azzam, Lindsay Hinck
Stem cells use mode of cell division, symmetric (SCD) versus asymmetric (ACD), to balance expansion with self-renewal and the generation of daughter cells with different cell fates. Studies in model organisms have identified intrinsic mechanisms that govern this process, which involves partitioning molecular components between daughter cells, frequently through the regulation of the mitotic spindle. Research performed in vertebrate tissues is revealing both conservation of these intrinsic mechanisms and crucial roles for extrinsic cues in regulating the frequency of these divisions...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/28391011/administration-of-sonic-hedgehog-protein-induces-angiogenesis-and-has-therapeutic-effects-after-stroke-in-rats
#9
Sheng-Cai Chen, Ming Huang, Quan-Wei He, Yan Zhang, Elvis Nana Opoku, Hang Yang, Hui-Juan Jin, Yuan-Peng Xia, Bo Hu
The Sonic hedgehog (Shh) signaling pathway is recapitulated in response to ischemic injury. Here, we investigated the clinical implications of Shh protein in the ischemic stroke and explored the underlying mechanism. Intracerebroventricular injection of Shh, Cyclopamine, or anti-vascular endothelial growth factor (VEGF) was performed immediately after permanent middle cerebral artery occlusion (pMCAO) surgery and lasted for 7days (d). Phosphate-buffered saline (PBS) was used as control. Neurological deficits and infarct volume were examined 7d after pMCAO...
April 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28390897/identification-and-characterization-of-two-novel-ptch1-splice-variants
#10
Pei Yu, Jinqing Yang, Yan Zhang
Patched-1 (PTCH1), one of the key molecules involved in the Hedgehog (HH) signaling pathway, acts as the receptor of the HH ligand. PTCH1 also inhibits the positive signal transducer Smoothened (SMO). Several PTCH1 splice variants have been identified and confirmed to play critical roles in HH pathway regulation. In the present study, two novel alternatively spliced variants of PTCH1 transcripts, designated PTCH1-Δ10 and PTCH1-Δ15, were found in humans, mice and zebrafish using RT-PCR, direct sequencing and ribonuclease protection assays...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28389227/restore-the-brake-on-tumor-progression
#11
REVIEW
Renata E Gordon, Li Zhang, Zeng-Jie Yang
Sonic hedgehog (Shh) signaling plays a key role in regulating normal development. The negative feedback mechanism mediated by the transcriptional factor, Gli3, acts to finely tune Shh signaling, providing tight control of normal developmental processes. Hyperactivation of Shh signaling often leads to many human malignancies, including basal cell carcinoma and medulloblastoma (MB). However, how tumor cells sustain the aberrant activation of Shh signaling is still not completely understood. We recently revealed that during MB formation, tumor cells express Nestin, a type VI intermediate filament protein, which maintains uncontrolled Shh signaling by abolishing negative feedback by Gli3...
April 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28387977/ex-vivo-analysis-of-the-contribution-of-fgf10-cells-to-airway-smooth-muscle-cell-formation-during-early-lung-development
#12
Elie El Agha, Vahid Kheirollahi, Alena Moiseenko, Werner Seeger, Saverio Bellusci
BACKGROUND: Airway smooth muscle cells (ASMCs) have been widely studied during embryonic lung development. These cells have been shown to control epithelial bifurcation during branching morphogenesis. Fibroblast growth factor 10-positive (FGF10(+) ) cells, originally residing in the submesothelial mesenchyme, contribute to ASMC formation in the distal lung. The reported work aims at monitoring the response of FGF10(+) progenitors and differentiated ASMCs to growth factor treatment in real time using lineage tracing in the background of an air-liquid interface culture system...
April 7, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28386245/molecular-mechanisms-of-stem-progenitor-cell-maintenance-in-the-adrenal-cortex
#13
REVIEW
Antonio Marcondes Lerario, Isabella Finco, Christopher LaPensee, Gary Douglas Hammer
The adrenal cortex is characterized by three histologically and functionally distinct zones: the outermost zona glomerulosa (zG), the intermediate zona fasciculata, and the innermost zona reticularis. Important aspects of the physiology and maintenance of the adrenocortical stem/progenitor cells have emerged in the last few years. Studies have shown that the adrenocortical cells descend from a pool of progenitors that are localized in the subcapsular region of the zG. These cells continually undergo a process of centripetal displacement and differentiation, which is orchestrated by several paracrine and endocrine cues, including the pituitary-derived adrenocorticotrophic hormone, and angiotensin II...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28382140/hedgehog-signaling-pathway-regulates-ovarian-cancer-invasion-and-migration-via-adhesion-molecule-cd24
#14
Chunyan Zeng, Tingtao Chen, Yan Zhang, Qi Chen
Hedgehog (Hh) signalling plays an important role in cancer; however, its mechanism in ovarian cancer migration and invasion remains unclear. In the present study, we aimed to clarify the effect of the Hh signalling pathway on ovarian cancer migration and invasion through the regulation of CD24 expression, both in vitro and in vivo. Patients with ovarian cancer (n = 97) were recruited for this study. Evaluation of the explored the role parameters of patients indicated that CD24 expression was negatively associated with age, histological type and lymph node metastasis (p>0...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28379718/sonic-hedgehog-signaling-regulates-myofibroblast-function-during-alveolar-septum-formation-in-murine-postnatal-lung
#15
Matthias C Kugler, Cynthia A Loomis, Zhicheng Zhao, Jennifer C Cushman, Li Liu, John S Munger
Sonic Hedgehog (Shh) signaling regulates mesenchymal proliferation and differentiation during embryonic lung development. In the adult lung, Shh signaling maintains mesenchymal quiescence and is dysregulated in diseases such as IPF and COPD. Our previous data implicated a role for Shh in postnatal lung development. Here we report a detailed analysis of Shh signaling during murine postnatal lung development. We show that Shh pathway expression and activity during alveolarization (P0-P14) are distinct from those during maturation (P14-P24)...
April 5, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28379564/shortened-primary-cilium-length-and-dysregulated-sonic-hedgehog-signaling-in-niemann-pick-c1-disease
#16
Sonia Canterini, Jessica Dragotto, Andrea Dardis, Stefania Zampieri, Maria Egle De Stefano, Franco Mangia, Robert P Erickson, Maria Teresa Fiorenza
The Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder due to mutations in the NPC1 gene, encoding a transmembrane protein related to the Sonic hedgehog receptor, Patched, and involved in intracellular trafficking of cholesterol. We have recently found that the proliferation of cerebellar granule neuron precursors is significantly reduced in Npc1-/- mice due to the downregulation of Shh expression. This finding prompted us to analyze the formation of the primary cilium, a non-motile organelle that is specialized for Shh signal transduction and responsible, when defective, for several human genetic disorders...
April 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28370639/transcriptional-activation-of-hedgehog-pathway-components-in-aggressive-hemangioma
#17
Danielle S Wendling-Keim, Lynn Wanie, Rainer Grantzow, Roland Kappler
Infantile hemangioma is a vascular neoplasm and is one of the most common tumors diagnosed in young children. Although most hemangiomas are harmless and involute spontaneously, some show severe progression, leading to serious complications, such as high output cardiac failure, ulcerations, compression of the trachea or deprivation amblyopia, depending on their size and localization. However, the pathogenesis and cause of hemangioma are largely unknown to date. The goal of this study was to identify markers that could predict hemangiomas with aggressive growth and severe progression that would benefit from early intervention...
March 31, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28367479/heterochronic-pellet-assay-to-test-cell-cell-communication-in-the-mouse-retina
#18
Nobuhiko Tachibana, Dawn Zinyk, Randy Ringuette, Valerie Wallace, Carol Schuurmans
All seven retinal cell types that make up the mature retina are generated from a common, multipotent pool of retinal progenitor cells (RPCs) (Wallace, 2011). One way that RPCs know when sufficient numbers of particular cell-types have been generated is through negative feedback signals, which are emitted by differentiated cells and must reach threshold levels to block additional differentiation of that cell type. A key assay to assess whether negative feedback signals are emitted by differentiated cells is a heterochronic pellet assay in which early stage RPCs are dissociated and labeled with BrdU, then mixed with a 20-fold excess of dissociated differentiated cells...
February 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28359846/long-term-effect-of-neonatal-inhibition-of-app-gamma-secretase-on-hippocampal-development-in-the-ts65dn-mouse-model-of-down-syndrome
#19
Fiorenza Stagni, Alessandra Raspanti, Andrea Giacomini, Sandra Guidi, Marco Emili, Elisabetta Ciani, Alessandro Giuliani, Andrea Bighinati, Laura Calzà, Jacopo Magistretti, Renata Bartesaghi
Neurogenesis impairment is considered a major determinant of the intellectual disability that characterizes Down syndrome (DS), a genetic condition caused by triplication of chromosome 21. Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations. In particular, excessive levels of AICD (amyloid precursor protein intracellular domain) resulting from APP cleavage by gamma-secretase increase the transcription of Ptch1, a Sonic Hedgehog (Shh) receptor that keeps the mitogenic Shh pathway repressed...
March 28, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28352167/changes-in-the-number-of-cd31-cd45-sca-1-cells-and-shh-signaling-pathway-involvement-in-the-lungs-of-mice-with-emphysema-and-relevant-effects-of-acute-adenovirus-infection
#20
Minhua Deng, Jinhua Li, Ye Gan, Yan Chen, Ping Chen
BACKGROUND: COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31(-)CD45(-)Sca-1(+) cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI)...
2017: International Journal of Chronic Obstructive Pulmonary Disease
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