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https://www.readbyqxmd.com/read/29784673/formation-of-the-sacrum-requires-down-regulation-of-sonic-hedgehog-signaling-in-the-sacral-intervertebral-discs
#1
Raffaella Bonavita, Kathleen Vincent, Robert Pinelli, Chitra Lekha Dahia
In humans, the sacrum forms an important component of the pelvic arch, and it transfers the weight of the body to the lower limbs. The sacrum is formed by collapse of the intervertebral discs (IVDs) between the five sacral vertebrae during childhood, and their fusion to form a single bone. We show that collapse of the sacral discs in the mouse is associated with the down-regulation of sonic hedgehog (SHH) signaling in the nucleus pulposus (NP) of the disc, and many aspects of this phenotype can be reversed by experimental postnatal activation of HH signaling...
May 21, 2018: Biology Open
https://www.readbyqxmd.com/read/29784581/how-to-make-a-tongue-cellular-and-molecular-regulation-of-muscle-and-connective-tissue-formation-during-mammalian-tongue-development
#2
REVIEW
Martyn T Cobourne, Sachiko Iseki, Anahid A Birjandi, Hadeel Adel Al-Lami, Christel Thauvin-Robinet, Guilherme M Xavier, Karen J Liu
The vertebrate tongue is a complex muscular organ situated in the oral cavity and involved in multiple functions including mastication, taste sensation, articulation and the maintenance of oral health. Although the gross embryological contributions to tongue formation have been known for many years, it is only relatively recently that the molecular pathways regulating these processes have begun to be discovered. In particular, there is now evidence that the Hedgehog, TGF-Beta, Wnt and Notch signaling pathways all play an important role in mediating appropriate signaling interactions between the epithelial, cranial neural crest and mesodermal cell populations that are required to form the tongue...
May 18, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29778738/risk-adapted-therapy-for-young-children-with-medulloblastoma-sjyc07-therapeutic-and-molecular-outcomes-from-a-multicentre-phase-2-trial
#3
Giles W Robinson, Vasilisa A Rudneva, Ivo Buchhalter, Catherine A Billups, Sebastian M Waszak, Kyle S Smith, Daniel C Bowers, Anne Bendel, Paul G Fisher, Sonia Partap, John R Crawford, Tim Hassall, Daniel J Indelicato, Frederick Boop, Paul Klimo, Noah D Sabin, Zoltan Patay, Thomas E Merchant, Clinton F Stewart, Brent A Orr, Jan O Korbel, David T W Jones, Tanvi Sharma, Peter Lichter, Marcel Kool, Andrey Korshunov, Stefan M Pfister, Richard J Gilbertson, Robert P Sanders, Arzu Onar-Thomas, David W Ellison, Amar Gajjar, Paul A Northcott
BACKGROUND: Young children with medulloblastoma have a poor overall survival compared with older children, due to use of radiation-sparing therapy in young children. Radiotherapy is omitted or reduced in these young patients to spare them from debilitating long-term side-effects. We aimed to estimate event-free survival and define the molecular characteristics associated with progression-free survival in young patients with medulloblastoma using a risk-stratified treatment strategy designed to defer, reduce, or delay radiation exposure...
May 16, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29777201/novel-smoothened-inhibitors-for-therapeutic-targeting-of-na%C3%A3-ve-and-drug-resistant-hedgehog-pathway-driven-cancers
#4
Qing-Rou Li, Hui Zhao, Xue-Sai Zhang, Henk Lang, Ker Yu
The G protein-coupled receptor (GPCR) smoothened (SMO) is a key signaling component of the sonic hedgehog (Hh) pathway and a clinically validated target for cancer treatment. The FDA-approved SMO inhibitors GDC-0449/Vismodegib and LDE225/Sonidegib demonstrated clinical antitumor efficacy. Nevertheless, relatively high percentage of treated patients would eventually develop acquired cross resistance to both drugs. Here, based on published structure and activity of GDC-0449 inhibitor class, we replaced its amide core with benzimidazole which retained bulk of the SMO-targeting activity as measured in our Hh/SMO/Gli1-reporter system...
May 18, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29776636/molecular-diagnostics-in-the-neoplasms-of-the-pancreas-liver-gallbladder-and-extrahepatic-biliary-tract-2018-update
#5
REVIEW
Lei Zhang, Martin H Bluth, Amarpreet Bhalla
Pancreatic neoplasms, including ductal adenocarcinoma, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and pancreatoblastoma, are associated with different genetic abnormalities. Hepatic adenomas with beta-catenin exon 3 mutation are associated with a high risk of malignancy. Hepatic adenoma with arginosuccinate synthetase 1 expression or sonic hedgehog mutations are associated with a risk of bleeding. Hepatocellular carcinoma and choangiocarcinoma display heterogeneity at both morphologic and molecular levels Cholangiocellular carcinoma is most commonly associated with IDH 1/2 mutations...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29776351/a-computational-study-of-hedgehog-signalling-involved-in-basal-cell-carcinoma-reveals-the-potential-and-limitation-of-combination-therapy
#6
Antoine Buetti-Dinh, Rebecca Jensen, Ran Friedman
BACKGROUND: The smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations. METHODS: We investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC...
May 18, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29773652/stromal-gli-signaling-regulates-the-activity-and-differentiation-of-prostate-stem-and-progenitor-cells
#7
Qianjin Li, Omar A Alsaidan, Sumit Rai, Meng Wu, Huifeng Shen, Zanna Beharry, Luciana L Almada, Martin E Fernandez-Zapico, Lianchun Wang, Houjian Cai
Interactions between cells in the stroma and epithelium facilitate prostate stem cell activity and tissue regeneration capacity. Numerous molecular signal transduction pathways, including the induction of sonic hedgehog (Shh) to activate the Gli transcription factors, are known to mediate the crosstalk of these two cellular compartments. However, the details of how these signaling pathways regulate prostate stem and progenitor cell activity remain elusive. Here we demonstrate that while cell autonomous epithelial Shh-Gli signaling is essential to determine the expression levels of basal cell markers and the renewal potential of epithelial stem and progenitor cells, stromal Gli signaling regulates prostate stem and progenitor cell activity by increasing the number and size of prostate spheroids in vitro...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29771958/cooperation-of-bmp-and-ihh-signaling-in-interdigital-cell-fate-determination
#8
Arunima Murgai, Sara Altmeyer, Stephanie Wiegand, Przemko Tylzanowski, Sigmar Stricker
The elaborate anatomy of hands and feet is shaped by coordinated formation of digits and regression of the interdigital mesenchyme (IM). A failure of this process causes persistence of interdigital webbing and consequently cutaneous syndactyly. Bone morphogenetic proteins (BMPs) are key inductive factors for interdigital cell death (ICD) in vivo. NOGGIN (NOG) is a major BMP antagonist that can interfere with BMP-induced ICD when applied exogenously, but its in vivo role in this process is unknown. We investigated the physiological role of NOG in ICD and found that Noggin null mice display cutaneous syndactyly and impaired interdigital mesenchyme specification...
2018: PloS One
https://www.readbyqxmd.com/read/29771176/potential-use-of-cxcl12-cxcr4-and-sonic-hedgehog-pathways-as-therapeutic-targets-in-medulloblastoma
#9
Marla Karine Amarante, Glauco Akelinghton Freire Vitiello, Marcos Henrique Rosa, Igor Alves Mancilla, Maria Angelica Ehara Watanabe
Medulloblastoma (MB) is the most common malignant brain tumor occurring in children, and although high long-term survival rates have been reached with current therapeutic protocols, several neurological injuries are still observed among survivors. It has been shown that the development of MB is highly dependent on the microenvironment surrounding it and that the CXCL12 chemokine and its receptor, CXCR4 and the Sonic Hedgehog (SHH) pathway are crucial for cerebellar development, coordinating proliferation and migration of embryonic cells and malfunctions in these axes can lead to MB development...
May 17, 2018: Acta Oncologica
https://www.readbyqxmd.com/read/29770198/recent-advances-in-managing-understanding-meningioma
#10
REVIEW
Nawal Shaikh, Karan Dixit, Jeffrey Raizer
Meningiomas are the most common adult primary intracranial tumor. Despite their higher incidence, there have not-until recently-been as many advances in understanding and managing meningiomas. Thus far, two broad classes of meningiomas have emerged on the basis of their mutational profile: those driven by neurofibromatosis 2 (NF2) inactivation and those with non-NF2 driver gene alterations, such as mammalian target of rapamycin and Hedgehog, Wingless/b-catenin, Notch, transforming growth factor-b receptor, mitogen-activated protein kinase, and phospholipase C pathway alterations...
2018: F1000Research
https://www.readbyqxmd.com/read/29768039/loss-of-sonic-hedgehog-gene-leads-to-muscle-development-disorder-and-megaesophagus-in-mice
#11
Xueting Jia, Li Min, Shengtao Zhu, Shutian Zhang, Xiaofeng Huang
Sonic hedgehog ( Shh) is crucial for organogenesis in the foregut. This study investigated the function of Shh at the late-gestational stage; during which, the esophagus continues to differentiate. We established cytokeratin 14 ( CK14)-Cre;Shhfl/fl mice in which the down-regulation of Shh in the epithelium occurred at approximately the same time as esophageal muscle conversion. Hematoxylin and eosin and immunohistochemical staining, with antibodies against keratin 14, Shh, patched 1 (Ptch1), Gli1, proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (αSMA), high-molecular-weight caldesmon (hCD), myogenin, paired box 7 (Pax7), β3-tubulin, and protein gene product 9...
May 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29765007/from-intra-to-extracellular-vesicles-extracellular-vesicles-in-developmental-signalling
#12
REVIEW
Ana-Citlali Gradilla, Eléanor Simon, Gustavo Aguilar, Isabel Guerrero
Signalling from cell-to-cell is fundamental for determining differentiation and patterning. This communication can occur between adjacent and distant cells. Extracellular vesicles (EVs) are membrane-based structures thought to facilitate the long-distance movement of signalling molecules. EVs have recently been found to allow the transport of two major developmental signalling pathways: Hedgehog and Wnt. These signalling molecules undergo crucial post-translational lipid modifications, which anchor them to membranes and impede their free release into the extracellular space...
May 15, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/29763457/overlap-in-signaling-between-smoothened-and-the-%C3%AE-subunit-of-the-heterotrimeric-g-protein-g13
#13
Xueshui Guo, Natalia A Riobo-Del Galdo, Eun Ji Kim, Gregory R Grant, David R Manning
The Hedgehog family of morphogens has long been known to utilize, through the 7-transmembrane protein Smoothened (Smo), the heterotrimeric G protein Gi in both canonical and noncanonical forms of signaling. Other G proteins, while not specifically utilized by Smo, may nonetheless provide access to some of the events controlled by it. We reported several years ago that the G protein G13 activates one or more forms of the Gli family of transcription factors. While the Gli transcription factors are well known targets for Smo, the uncertain mechanism of activation by G13 and the identity of the targeted Gli(s) limited predictions as to the extent to which G13 might mimic Smo's actions...
2018: PloS One
https://www.readbyqxmd.com/read/29762916/painful-circumscribed-bullous-dermatosis-of-the-left-hand-after-contact-with-african-four-toed-hedgehogs
#14
Silke Gebauer, Silke Uhrlass, Daniela Koch, Constanze Krüger, Nadine Rahmig, Uta-Christina Hipler, Pietro Nenoff
No abstract text is available yet for this article.
May 15, 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/29760872/giant-morphea-form-basal-cell-carcinoma-of-the-umbilicus-successful-debulking-with-vismodegib
#15
Mariana Orduz Robledo, Eve Lebas, Marie-Annick Reginster, Mahmoud Baghaie, Sabine Groves, Arjen F Nikkels
Basal cell carcinoma of the umbilicus is very rare. The nodular subtype is the main representative. Giant basal cell carcinomas represent around 1% of all basal cell carcinomas. The hedgehog pathway inhibitor vismodegib is indicated for advanced basal cell carcinoma and CD56-negative immunostaining seems indicative for successful treatment. A 54-year-old man presented a 10 cm × 14 cm large and 4.5 cm deep morphea-form basal cell carcinoma with faint immunohistochemical CD56 expression arising from the umbilicus...
2018: Rare Tumors
https://www.readbyqxmd.com/read/29760202/survey-of-human-chromosome-21-gene-expression-effects-on-early-development-in-danio-rerio
#16
Sarah Edie, Norann A Zaghloul, Carmen C Leitch, Donna K Klinedinst, Janette Lebron, Joey F Thole, Andrew S McCallion, Nicholas Katsanis, Roger H Reeves
Trisomy for human chromosome 21 (Hsa21) results in Down syndrome (DS), one of the most genetically complex conditions compatible with human survival. Assessment of the physiological consequences of dosage-driven overexpression of individual Hsa21 genes during early embryogenesis and the resulting contributions to DS pathology in mammals are not tractable in a systematic way. A recent study looked loss-of-function of C. elegans orthologues of Hsa21 genes and identified ten candidates with behavioral phenotypes, but the equivalent over-expression experiment has not been done...
May 14, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29756778/omnidispersible-hedgehog-particles-with-multilayer-coatings-for-multiplexed-biosensing
#17
Douglas G Montjoy, Joong Hwan Bahng, Aydin Eskafi, Harrison Hou, Nicholas A Kotov
Hedgehog particles (HPs) replicating the spiky geometry of pollen grains revealed surprisingly high dispersion stability regardless of whether their hydrophobicity/hydrophilicity matches that of the media or not. This property designated as omnidispersibility, is attributed to the drastic reduction of van der Waals interactions between particles coated with stiff nanoscale spikes compared to particles of the same dimensions with smooth surfaces. One may hypothesize but it remains unknown, however, whether HPs modified with polymers or nanoparticles (NPs) would retain this property...
May 14, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29754802/intracellular-calcium-mobilization-is-required-for-sonic-hedgehog-signaling
#18
Dana Klatt Shaw, Derrick Gunther, Michael J Jurynec, Alexis A Chagovetz, Erin Ritchie, David Jonah Grunwald
Graded Shh signaling across fields of precursor cells coordinates patterns of gene expression, differentiation, and morphogenetic behavior as precursors form complex structures, such as the nervous system, the limbs, and craniofacial skeleton. Here we discover that intracellular calcium mobilization, a process tightly controlled and readily modulated, regulates the level of Shh-dependent gene expression in responding cells and affects the development of all Shh-dependent cell types in the zebrafish embryo. Reduced expression or modified activity of ryanodine receptor (RyR) intracellular calcium release channels shifted the allocation of Shh-dependent cell fates in the somitic muscle and neural tube...
May 8, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29749693/modeling-the-complex-etiology-of-holoprosencephaly-in-mice
#19
Mingi Hong, Robert S Krauss
Holoprosencephaly (HPE) is a common developmental defect caused by failure to define the midline of the forebrain and/or midface. HPE is associated with heterozygous mutations in Nodal and Sonic hedgehog (SHH) pathway components, but clinical presentation is highly variable, and many mutation carriers are unaffected. It is therefore thought that such mutations interact with more common modifiers, genetic and/or environmental, to produce severe patterning defects. Modifiers are difficult to identify, as their effects are context-dependent and occur within the complex genetic and environmental landscapes that characterize human populations...
May 11, 2018: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/29749689/functions-of-tgif-homeodomain-proteins-and-their-roles-in-normal-brain-development-and-holoprosencephaly
#20
David Wotton, Kenichiro Taniguchi
Holoprosencephaly (HPE) is a frequent human forebrain developmental disorder with both genetic and environmental causes. Multiple loci have been associated with HPE in humans, and potential causative genes at 14 of these loci have been identified. Although TGIF1 (originally TGIF, for Thymine Guanine-Interacting Factor) is among the most frequently screened genes in HPE patients, an understanding of how mutations in this gene contribute to the pathogenesis of HPE has remained elusive. However, mouse models based on loss of function of Tgif1, and the related Tgif2 gene, have shed some light on how human TGIF1 variants might cause HPE...
May 11, 2018: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
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