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https://www.readbyqxmd.com/read/29330329/large-genomic-insertion-at-the-shh-locus-results-in-hammer-toes-through-enhancer-adoption
#1
Christina Paliou, Guillaume Andrey
No abstract text is available yet for this article.
January 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29329593/targeting-ectodysplasin-promotor-by-crispr-dcas9-effector-effectively-induces-the-reprogramming-of-human-bone-marrow-derived-mesenchymal-stem-cells-into-sweat-gland-like-cells
#2
Sujing Sun, Jun Xiao, Jiahui Huo, Zhijun Geng, Kui Ma, Xiaoyan Sun, Xiaobing Fu
BACKGROUND: Patients with a deep burn injury are characterized by losing the function of perspiration and being unable to regenerate the sweat glands. Because of their easy accession, multipotency, and lower immunogenicity, bone marrow-derived mesenchymal stem cells (BM-MSCs) represent as an ideal biological source for cell therapy. The aim of this study was to identify whether targeting the promotor of ectodysplasin (EDA) by CRISPR/dCas9-effector (dCas9-E) could induce the BM-MSCs to differentiate into sweat gland-like cells (SGCs)...
January 12, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29329585/involvement-of-hedgehog-pathway-in-early-onset-aggressive-molecular-subtypes-and-metastatic-potential-of-breast-cancer
#3
Syeda Kiran Riaz, Jahangir Sarwar Khan, Syed Tahir Abbas Shah, Fen Wang, Lin Ye, Wen G Jiang, Muhammad Faraz Arshad Malik
BACKGROUND: Dysregulation of hedgehog pathway is observed in numerous cancers. Relevance of hedgehog pathway genes in cancer cohort and inhibition of its downstream effector (GLI1) towards metastasis in cell lines are explored in the study. METHOD: One hundred fifty fresh tumours of breast cancer patients were collected for the study. Based on differential expression, panel of 6 key regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray datasets were identified...
January 8, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29329447/congenital-hyperinsulinism-and-hypopituitarism-attributable-to-a-novel-mutation-in-foxa2
#4
Mary Ellen Vajravelu, Jinghua Chai, Bryan Krock, Samuel Baker, David Langdon, Craig Alter, Diva D De León
Context: Persistent hypoglycemia in the newborn period most commonly occurs due to hyperinsulinism. The phenotype of hypoketotic hypoglycemia can also result from pituitary hormone deficiencies, including growth hormone and adrenocorticotropic hormone deficiency. Forkhead box A2 (Foxa2) is a transcription factor shown in mouse models to influence insulin secretion by pancreatic beta cells. In addition, Foxa2 is involved in regulation of pituitary development, and deletions of FOXA2 have been linked to panhypopituitarism...
January 10, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29329377/endometrial-stem-cell-derived-g-csf-attenuates-endometrial-fibrosis-via-sonic-hedgehog-transcriptional-activator-gli2
#5
Xiaona Lin, Yanling Zhang, Yibin Pan, Shilin He, Yongdong Dai, Bingqing Zhu, Cheng Wei, Liaobing Xin, Wenzhi Xu, Chunsheng Xiang, Songying Zhang
Intrauterine adhesion (IUA) is characterized by endometrial fibrosis, which ultimately leads to menstrual abnormalities, infertility and recurrent miscarriages. The Shh/Gli2 pathway plays a critical role in tissue fibrogenesis and regeneration; Gli2 activation induces profibrogenic effects in various tissues, such as the liver and kidney. However, the role of Gli2 in endometrial fibrosis remains unknown. The purpose of this study was to test the hypothesis that activated Gli2 promotes endometrial fibrosis. Endometrial samples from moderate and severe IUA patients exhibited significantly enhanced expression of Gli2 compared with normal endometrial samples and mild IUA samples...
January 10, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29325895/the-vertebrate-limb-an-evolving-complex-of-self-organizing-systems
#6
REVIEW
Stuart A Newman, Tilmann Glimm, Ramray Bhat
The paired appendages (fins or limbs) of jawed vertebrates contain an endoskeleton consisting of nodules, bars and, in some groups, plates of cartilage, or bone arising from replacement of cartilaginous templates. The generation of the endoskeletal elements occurs by processes involving production and diffusion of morphogens, with, variously, positive and negative feedback circuits, adhesion, and receptor dynamics with similarities to the mechanism for chemical pattern formation proposed by Alan Turing. This review presents a unified interpretation of the evolution and functioning of these mechanisms...
January 8, 2018: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/29321670/clinical-and-experimental-evidence-suggest-a-link-between-kif7-and-c5orf42-related-ciliopathies-through-sonic-hedgehog-signaling
#7
Reza Asadollahi, Justin E Strauss, Martin Zenker, Oliver Beuing, Simon Edvardson, Orly Elpeleg, Tim M Strom, Pascal Joset, Dunja Niedrist, Christine Otte, Beatrice Oneda, Paranchai Boonsawat, Silvia Azzarello-Burri, Deborah Bartholdi, Michael Papik, Markus Zweier, Cordula Haas, Arif B Ekici, Alessandra Baumer, Eugen Boltshauser, Katharina Steindl, Michael Nothnagel, Albert Schinzel, Esther T Stoeckli, Anita Rauch
Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental disorder caused by KIF7 defects and belongs to the heterogeneous group of ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism, facial dysmorphism has not been emphasized in JBTS cohorts with molecular diagnosis. To evaluate the specificity and etiology of ACLS craniofacial features, we performed whole exome or targeted Sanger sequencing in patients with the aforementioned overlapping craniofacial appearance but variable additional ciliopathy features followed by functional studies...
January 10, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#8
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29314724/genipin-cross-linked-type-ii-collagen-scaffold-promotes-the-differentiation-of-adipose-derived-stem-cells-into-nucleus-pulposus-like-cells
#9
Xiaopeng Zhou, Yiqing Tao, Erman Chen, Jingkai Wang, Weijing Fang, Tengfei Zhao, Chengzhen Liang, Fangcai Li, Qixin Chen
Adipose-derived stem cells (ADSCs)-based tissue engineering was a promising method to treat intervertebral disc degeneration. Type II collagen is a native component in the nucleus pulposus (NP), and has the ability to promote ADSCs to differentiate into NP-like cells. In this article, we aimed to establish a genipin-cross-linked three-dimensional (3D) type II collagen scaffold, and determine the biological effects of the scaffold on ADSCs differentiating into a NP-like phenotype. Different concentrations of genipin were used to cross-link the 3D type II collagen scaffold...
January 3, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29313231/relationship-between-hedgehog-signaling-pathway-and-drug-resistance-of-poorly-differentiated-gliomas
#10
S A Cherepanov, N F Grinenko, O M Antonova, P B Kurapov, I I Shepeleva, V P Chekhonin
The effects of Hedgehog signaling inhibitor (cyclopamine) and activator (Shh) on drug resistance of U251-MG human glioma cells and human astrocyte culture to cisplatin, temozolomide, and doxorubicin were studied. Cyclopamine and Shh modified the drug resistance of U251-MG cells but not of human astrocytes. Experiments with cyclopamine, Shh, and chemical drugs can contribute to detection of the mechanisms of signaling effects on the drug resistance processes, while the experimental data can serve as one of the criteria for choosing individual chemotherapy for patients...
January 8, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29304494/sinomenine-reduces-growth-and-metastasis-of-breast-cancer-cells-and-improves-the-survival-of-tumor-bearing-mice-through-suppressing-the-shh-pathway
#11
Lingqin Song, Di Liu, Yang Zhao, Jianjun He, Huafeng Kang, Zhijun Dai, Xijing Wang, Shuqun Zhang, Ying Zan, Xinghuan Xue
In this study, the suppressive effect of sinomenine on the activation of SHh and the progression of breast cancer metastasis in vitro and in vivo was investigated. MDA-MB-231 breast cancer cells were treated with sinomenine and/or cyclopamine a proven SHh inhibitor. Sinomenine and cyclopamine both suppressed cell proliferation and migration, but sinomenine had a stronger suppressive effect in MDA-MB-231. In addition, sinomenine could suppress the activation of NF-κB and SHh signaling pathways, but cyclopamine could not suppress the activation of NF-κB...
January 2, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29302051/genetic-mapping-of-molar-size-relations-identifies-inhibitory-locus-for-third-molars-in-mice
#12
Nicolas Navarro, A Murat Maga
Molar size in Mammals shows considerable disparity and exhibits variation similar to that predicted by the Inhibitory Cascade model. The importance of such developmental systems in favoring evolutionary trajectories is also underlined by the fact that this model can predict macroevolutionary patterns. Using backcross mice, we mapped QTL for molar sizes controlling for their sequential development. Genetic controls for upper and lower molars appear somewhat similar, and regions containing genes implied in dental defects drive this variation...
January 5, 2018: Heredity
https://www.readbyqxmd.com/read/29299122/wnt-%C3%AE-catenin-and-hedgehog-pathways-are-involved-in-the-inflammatory-effect-of-interleukin-18-on-rat-chondrocytes
#13
Jiapeng Bao, Chiyuan Ma, Jisheng Ran, Yan Xiong, Shigui Yan, Lidong Wu
To investigate the inflammatory effect of Interleukin 18 (IL-18) on rat chondrocytes and the involvement of Wnt/β-catenin and Hedgehog pathways, the mRNA and protein level of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and chondrocyte-specific proteins (Collagen II and aggrecan) were evaluated by qRT-PCR and Western blot, and key protein level of Wnt/β-catenin and Hedgehog pathways including β-catenin, GSK-3β, DKK-1, IHH, SHH, and Gli-2 were evaluated by Western blot. Dickkopf-1 (DKK-1) and Cyclopamine were used as antagonist of Wnt/β-catenin and Hedgehog pathways to perform pathway inhibition tests...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295693/novel-homeodomain-transcription-factor-nkx2-2-in-the-brain-tumor-development
#14
Mubeena Pm Mariyath, Mehdi Hayat Shahi, Shirin Farheen, Mohd Tayyab, Nabeela Khanam, Asif Ali
BACKGROUND: Complex central nervous system (CNS) is made of neuronal cells and glial cells. Cells of central nervous system are able to regenerate after injury and during repairing. Sonic hedgehog pathway initiated by Shh-N a glycoprotein plays vital role in CNS patterning growth, development and now tumorigenesis. Nkx2.2 homeodomain transcription factor is an effecter molecule, which is positively regulated by Shh during normal growth. Nkx2.2 is essential for V3 domain specification during neural tube patterning at embryonic stage...
January 1, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29290584/crispr-screens-uncover-genes-that-regulate-target-cell-sensitivity-to-the-morphogen-sonic-hedgehog
#15
Ganesh V Pusapati, Jennifer H Kong, Bhaven B Patel, Arunkumar Krishnan, Andreas Sagner, Maia Kinnebrew, James Briscoe, L Aravind, Rajat Rohatgi
To uncover regulatory mechanisms in Hedgehog (Hh) signaling, we conducted genome-wide screens to identify positive and negative pathway components and validated top hits using multiple signaling and differentiation assays in two different cell types. Most positive regulators identified in our screens, including Rab34, Pdcl, and Tubd1, were involved in ciliary functions, confirming the central role for primary cilia in Hh signaling. Negative regulators identified included Megf8, Mgrn1, and an unannotated gene encoding a tetraspanin protein we named Atthog...
December 26, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29285739/sonic-hedgehog-regulation-of-the-neural-precursor-cell-fate-during-chicken-optic-tectum-development
#16
Ciqing Yang, Xiaoying Li, Qiuling Li, Han Li, Liang Qiao, Zhikun Guo, Juntang Lin
During nervous system development, neurons project axons over long distances to reach the appropriate targets for correct neural circuit formation. Sonic hedgehog (Shh) is a secreted protein and plays a key role in regulating vertebrate embryogenesis, especially in central nervous system (CNS) patterning, including neuronal migration and axonal projection in the brain and spinal cord. In the developing ventral midbrain, Shh is sufficient to specify a striped pattern of cell fates. Little is known about the molecular mechanisms underlying the Shh regulation of the neural precursor cell fate during the optic tectum development...
December 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29285189/sulforaphane-reverses-gefitinib-tolerance-in-human-lung-cancer-cells-via-modulation-of-sonic-hedgehog-signaling
#17
Fanping Wang, Wenjun Wang, Junpeng Li, Jingjing Zhang, Xia Wang, Mingyong Wang
Gefitinib is a targeted anticancer drug that was developed as an effective clinical therapy for lung cancer. Numerous patients develop gefitinib resistance in response to treatment. Sulforaphane (SFN) is present in cruciferous vegetables, and has been demonstrated to inhibit the malignant growth of various types of cancer cells. To investigate the role of SFN in gefitinib resistance, a gefitinib-tolerant PC9 (PC9GT) cell model was established by continually exposing PC9 cells to gefitinib. Cell viability was measured using a cell proliferation assay...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29284139/coordinated-d-cyclin-foxd1-activation-drives-mitogenic-activity-of-sonic-hedgehog-signaling-pathway
#18
Dustin M Fink, Miranda R Sun, Galen W Heyne, Joshua L Everson, Hannah M Chung, Sookhee Park, Michael D Sheets, Robert J Lipinski
Sonic Hedgehog (Shh) signaling plays key regulatory roles in embryonic development and postnatal homeostasis and repair. Modulation of the Shh pathway is known to cause malformations and malignancies associated with dysregulated tissue growth. However, our understanding of the molecular mechanisms by which Shh regulates cellular proliferation is incomplete. Here, using mouse embryonic fibroblasts, we demonstrate that the Forkhead box gene Foxd1 is transcriptionally regulated by canonical Shh signaling and required for downstream proliferative activity...
December 25, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29280516/suppression-of-stat3-nh2-terminal-domain-chemosensitizes-medulloblastoma-cells-by-activation-of-protein-inhibitor-of-activated-stat3-via-de-repression-by-microrna-21
#19
Sutapa Ray, Don W Coulter, Shawn D Gray, Jason A Sughroue, Shrabasti Roychoudhury, Erin M McIntyre, Nagendra K Chaturvedi, Kishor K Bhakat, Shantaram S Joshi, Timothy R McGuire, John G Sharp
Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription-3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3-NH2 terminal domain inhibitor (S3-NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/SHH tumors...
December 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29279401/neuronal-delivery-of-hedgehog-directs-spatial-patterning-of-taste-organ-regeneration
#20
Wan-Jin Lu, Randall K Mann, Allison Nguyen, Tingting Bi, Max Silverstein, Jean Y Tang, Xiaoke Chen, Philip A Beachy
How organs maintain and restore functional integrity during ordinary tissue turnover or following injury represents a central biological problem. The maintenance of taste sensory organs in the tongue was shown 140 years ago to depend on innervation from distant ganglion neurons, but the underlying mechanism has remained unknown. Here, we show that Sonic hedgehog (Shh), which encodes a secreted protein signal, is expressed in these sensory neurons, and that experimental ablation of neuronal Shh expression causes loss of taste receptor cells (TRCs)...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
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