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Sonic hedgehog

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https://www.readbyqxmd.com/read/28296537/microfluidic-mobility-shift-assay-for-real-time-analysis-of-peptide-n-palmitoylation
#1
Thomas Lanyon-Hogg, Neki V Patel, Markus Ritzefeld, Katherine J Boxall, Rosemary Burke, Julian Blagg, Anthony I Magee, Edward W Tate
The Hedgehog pathway is a key developmental signaling pathway but is also implicated in many types of cancer. The extracellular signaling protein Sonic hedgehog (Shh) requires dual lipidation for functional signaling, whereby N-terminal palmitoylation is performed by the enzyme Hedgehog acyltransferase (Hhat). Hhat is an attractive target for small-molecule inhibition to arrest Hedgehog signaling, and methods for assaying Hhat activity are central to understanding its function. However, all existing assays to quantify lipidation of peptides suffer limitations, such as safety hazards, high costs, extensive manual handling, restriction to stopped-assay measurements, or indirect assessment of lipidation...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28293554/sonic-hedgehog-signaling-in-limb-development
#2
REVIEW
Cheryll Tickle, Matthew Towers
The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28286175/cilia-dependent-gli-processing-in-neural-crest-cells-is-required-for-tongue-development
#3
Grethel Millington, Kelsey Elliott, Ya-Ting Chang, Ching-Fang Chang, Andrzej Dlugosz, Samantha A Brugmann
Ciliopathies are a class of diseases caused by the loss of a ubiquitous, microtubule-based organelle called a primary cilium. Ciliopathies commonly result in defective development of the craniofacial complex, causing midfacial defects, craniosynostosis, micrognathia and aglossia. Herein, we explored how the conditional loss of primary cilia on neural crest cells (Kif3a(f/f);Wnt1-Cre) generated aglossia. On a cellular level, our data revealed that aglossia in Kif3a(f/f);Wnt1-Cre embryos was due to a loss of mesoderm-derived muscle precursors migrating into and surviving in the tongue anlage...
March 9, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28280721/tissue-biomarkers-in-hepatocellular-tumors-which-when-and-how
#4
REVIEW
Luca Di Tommaso, Massimo Roncalli
Few tissue markers are currently available to pathologists in the study of hepatocellular tumors. These markers should be used carefully taking into consideration not only morphology but also, and sometimes even more important, the clinical setting where the lesion to be diagnosed had developed. Glypican-3, heat shock protein 70, and glutamine synthetase (GS) are markers currently used, as a single panel, to discriminate the nature of a <2 cm hepatocellular lesion lacking radiological features of hepatocellular carcinoma (HCC) detected in a cirrhotic patient under surveillance...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28275687/hedgehog-signaling-links-chronic-inflammation-to-gastric-cancer-precursor-lesions
#5
REVIEW
Juanita L Merchant, Lin Ding
Since its initial discovery in Drosophila, Hedgehog (HH) signaling has long been associated with foregut development. The mammalian genome expresses 3 HH ligands, with sonic hedgehog (SHH) levels highest in the mucosa of the embryonic foregut. More recently, interest in the pathway has shifted to improving our understanding of its role in gastrointestinal cancers. The use of reporter mice proved instrumental in our ability to probe the expression pattern of SHH ligand and the cell types responding to canonical HH signaling during homeostasis, inflammation, and neoplastic transformation...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28273832/more-insight-into-bdnf-against-neurodegeneration-anti-apoptosis-anti-oxidation-and-suppression-of-autophagy
#6
REVIEW
Shang-Der Chen, Chia-Lin Wu, Wei-Chao Hwang, Ding-I Yang
In addition to its well-established neurotrophic action, brain-derived neurotrophic factor (BDNF) also possesses other neuroprotective effects including anti-apoptosis, anti-oxidation, and suppression of autophagy. We have shown before that BDNF triggers multiple mechanisms to confer neuronal resistance against 3-nitropropionic acid (3-NP)-induced mitochondrial dysfunction in primary rat cortical cultures. The beneficial effects of BDNF involve the induction of anti-oxidative thioredoxin with the resultant expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) as well as erythropoietin (EPO)-dependent stimulation of sonic hedgehog (SHH)...
March 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28270602/integration-of-shh-and-fgf-signaling-in-controlling-hox-gene-expression-in-cultured-limb-cells
#7
Alan R Rodrigues, Nayuta Yakushiji-Kaminatsui, Yuji Atsuta, Guillaume Andrey, Patrick Schorderet, Denis Duboule, Clifford J Tabin
During embryonic development, fields of progenitor cells form complex structures through dynamic interactions with external signaling molecules. How complex signaling inputs are integrated to yield appropriate gene expression responses is poorly understood. In the early limb bud, for instance, Sonic hedgehog (Shh) is expressed in the distal posterior mesenchyme, where it acts as a mediator of anterior to posterior (AP) patterning, whereas fibroblast growth factor 8 (Fgf8) is produced by the apical ectodermal ridge (AER) at the distal tip of the limb bud to direct outgrowth along the proximal to distal (PD) axis...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263766/shh-e176-e177-zn-2-conformation-is-required-for-signaling-at-endogenous-sites
#8
Diana S Himmelstein, Ivelisse Cajigas, Chunming Bi, Brian S Clark, Grant Van Der Voort, Jhumku D Kohtz
Sonic hedgehog (SHH) is a master developmental regulator. In 1995, the SHH crystal structure predicted that SHH-E176 (human)/E177 (mouse) regulates signaling through a Zn(2+)-dependent mechanism. While Zn(2+) is known to be required for SHH protein stability, a regulatory role for SHH-E176 or Zn(2+) has not been described. Here, we show that SHH-E176/177 modulates Zn(2+)-dependent cross-linking in vitro and is required for endogenous signaling, in vivo. While ectopically expressed SHH-E176A is highly active, mice expressing SHH-E177A at endogenous sites (Shh(E177A/-)) are morphologically indistinguishable from mice lacking SHH (Shh(-/-)), with patterning defects in both embryonic spinal cord and forebrain...
March 2, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28262835/high-frequency-stimulation-induces-sonic-hedgehog-release-from-hippocampal-neurons
#9
Yujuan Su, Yuan Yuan, Shengjie Feng, Shaorong Ma, Yizheng Wang
Sonic hedgehog (SHH) as a secreted protein is important for neuronal development in the central nervous system (CNS). However, the mechanism about SHH release remains largely unknown. Here, we showed that SHH was expressed mainly in the synaptic vesicles of hippocampus in both young postnatal and adult rats. High, but not low, frequency stimulation, induces SHH release from the neurons. Moreover, removal of extracellular Ca(2+), application of tetrodotoxin (TTX), an inhibitor of voltage-dependent sodium channels, or downregulation of soluble n-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) proteins, all blocked SHH release from the neurons in response to HFS...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261216/smoothened-regulates-migration-of-fibroblast-like-synoviocytes-in-rheumatoid-arthritis-via-activation-of-rho-gtpase-signaling
#10
Wei-Xiang Peng, Shang-Ling Zhu, Bai-Yu Zhang, Yi-Ming Shi, Xiao-Xue Feng, Fang Liu, Jian-Lin Huang, Song Guo Zheng
Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28260041/metformin-suppresses-the-expression-of-sonic-hedgehog-in-gastric-cancer-cells
#11
Zhou Song, Bo Wei, Canrong Lu, Xiaohui Huang, Peiyu Li, Lin Chen
The traditional anti-diabetic drug, metformin, has been found to have anticancer effects. The Sonic hedgehog (Shh) signaling pathway is involved in the on cogenesis of gastric cancer. The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells. HGC‑27 and MKN‑45 human gastric cancer cells were treated with metformin at different concentrations and for different durations. Subsequently the mRNA and protein levels of Shh, Smoothened (SMO), and Glioma‑associated oncogene (Gli)‑1, Gli‑2 and Gli‑3 were examined using western blot and reverse transcription‑quantitative polymerase chain reaction analyses...
February 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28251217/lymphangiogenesis-and-colorectal-cancer
#12
Ciyou Huang, Yigang Chen
Lymphatic metastasis is an important event in the progress of metastasis in colorectal cancer (CRC). The purpose of this article is to assess the role of lymphangiogenesis on CRC. In peritumoral areas of CRC, the lymphatic microvessel density (LMVD) is higher than those in normal colorectal tissues. Morever, the high LMVD is correlated with DFS and local recurrence in CRC. The VEGF-C/VEGF-D/VEGFR-3 pathway, sonic hedgehog (Shh) signaling pathway and extracellular matrix (ECM) are involved in the regulation of lymphangiogenesis in CRC...
March 2017: Saudi Medical Journal
https://www.readbyqxmd.com/read/28250409/ontogenetic-establishment-of-order-specific-nuclear-organization-in-the-mammalian-thalamus
#13
Wei Shi, Anjin Xianyu, Zhi Han, Xing Tang, Zhizhong Li, Haining Zhong, Tianyi Mao, Kun Huang, Song-Hai Shi
The thalamus connects the cortex with other brain regions and supports sensory perception, movement, and cognitive function via numerous distinct nuclei. However, the mechanisms underlying the development and organization of diverse thalamic nuclei remain largely unknown. Here we report an intricate ontogenetic logic of mouse thalamic structures. Individual radial glial progenitors in the developing thalamus actively divide and produce a cohort of neuronal progeny that shows striking spatial configuration and nuclear occupation related to functionality...
February 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28250200/cxcl14-is-a-candidate-biomarker-for-hedgehog-signalling-in-idiopathic-pulmonary-fibrosis
#14
Guiquan Jia, Sanjay Chandriani, Alexander R Abbas, Daryle J DePianto, Elsa N N'Diaye, Murat B Yaylaoglu, Heather M Moore, Ivan Peng, Jason DeVoss, Harold R Collard, Paul J Wolters, Jackson G Egen, Joseph R Arron
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. METHODS: We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor...
March 1, 2017: Thorax
https://www.readbyqxmd.com/read/28248256/integrated-proteomic-and-transcriptomic-based-approaches-to-identifying-signature-biomarkers-and-pathways-for-elucidation-of-daoy-and-uw228-subtypes
#15
Roger Higdon, Jessie Kala, Devan Wilkins, Julia Fangfei Yan, Manveen K Sethi, Liang Lin, Siqi Liu, Elizabeth Montague, Imre Janko, John Choiniere, Natali Kolker, William S Hancock, Eugene Kolker, Susan Fanayan
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Patient survival has remained largely the same for the past 20 years, with therapies causing significant health, cognitive, behavioral and developmental complications for those who survive the tumor. In this study, we profiled the total transcriptome and proteome of two established MB cell lines, Daoy and UW228, using high-throughput RNA sequencing (RNA-Seq) and label-free nano-LC-MS/MS-based quantitative proteomics, coupled with advanced pathway analysis...
February 3, 2017: Proteomes
https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#16
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28223149/long-term-behavioral-change-as-a-result-of-acute-ethanol-exposure-in-zebrafish-evidence-for-a-role-for-sonic-hedgehog-but-not-retinoic-acid-signaling
#17
Derek F Burton, Chengjin Zhang, Oswald Boa-Amponsem, Shanta Mackinnon, Gregory J Cole
BACKGROUND: Developmental exposure to ethanol is recognized to produce long-term neurobehavioral impairment in multiple animal models. However, the molecular mechanisms underlying these deficits remain poorly understood. The present study was undertaken to ascertain whether two well-characterized targets of prenatal alcohol exposure, sonic hedgehog (Shh) and retinoic acid (RA), that induce the hallmark morphological phenotypes of fetal alcohol spectrum disorders (FASD), are involved in the generation of behavioral alterations as a result of alcohol exposure...
February 20, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28218785/inhibition-of-shh-pathway-mechanisms-by-arsenic-trioxide-in-pediatric-medulloblastomas-a-comprehensive-literature-review
#18
REVIEW
P H S Klinger, A F Andrade, L E A Delsin, R G P Queiroz, C A Scrideli, L G Tone, E T Valera
Recent innovations in the genomic understanding of medulloblastomas have provided new ways to explore this highly invasive malignant brain cancer arising from the cerebellum. Among the four different medulloblastoma subgroups described to date, the sonic hedgehog (SHH) genetic pathway is the pathway activated in the tumorigenesis of medulloblastoma. SHH-related medulloblastomas are usually of nodular/desmoplastic histology and frequently occur in children under the age of three, an age group highly susceptible to the acute and long-term effects of treatment...
February 16, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28215635/mechanical-stimulation-promote-the-osteogenic-differentiation-of-bone-marrow-stromal-cells-through-epigenetic-regulation-of-sonic-hedgehog
#19
Chuandong Wang, Shengzhou Shan, Chenglong Wang, Jing Wang, Jiao Li, Guoli Hu, Kerong Dai, Qingfeng Li, Xiaoling Zhang
Mechanical unloading leads to bone loss and disuse osteoporosis partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro. Besides, we found that Hedgehog (Hh) signaling pathway was activated in this process. Inhibition of which by either knockdown of Sonic hedgehog (Shh) or treating BMSCs with Hh inhibitors attenuated the osteogenic effect of CMS on BMSCs, suggesting that Hh signaling pathway acts as an endogenous mediator of mechanical stimuli on BMSCs...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28205381/the-clinical-significance-of-equivocal-findings-on-spinal-mri-in-children-with-medulloblastoma
#20
Julie Bennett, Ramy Ashmawy, Vijay Ramaswamy, Derek Stephens, Eric Bouffet, Normand Laperriere, Michael Taylor, Manohar Shroff, Ute Bartels
BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood, with cerebrospinal fluid spread the most common site of metastasis. Currently, children diagnosed with MB and evidence of spinal metastasis are treated with an increased dose of craniospinal radiation (CSI). This report reviewed equivocal abnormalities including nerve root clumping, linear vascular enhancement, nerve root enhancement and/or other vague findings on spinal magnetic resonance imaging (MRI) to elucidate their prognostic significance and aid in risk stratification...
February 16, 2017: Pediatric Blood & Cancer
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