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https://www.readbyqxmd.com/read/28533268/the-transcription-factor-gli3-promotes-b-cell-development-in-fetal-liver-through-repression-of-shh
#1
Anisha Solanki, Ching-In Lau, José Ignacio Saldaña, Susan Ross, Tessa Crompton
Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])-deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs...
May 22, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28525403/genetic-diseases-associated-with-an-increased-risk-of-skin-cancer-development-in-childhood
#2
Alexander L Fogel, Kavita Y Sarin, Joyce M C Teng
PURPOSE OF REVIEW: Childhood skin cancers are relatively rare and may indicate an underlying genetic disorder. The increasing elucidation of genetic pathways is changing the diagnosis and management of genetic skin cancer susceptibility syndromes. In this review, we provide an overview of genetic conditions that predispose to skin cancer development in childhood and signs that providers should assess when evaluating affected individuals. RECENT FINDINGS: In basal cell nevus syndrome (BCNS), the patched2 (PTCH2) and suppressor of fused (SUFU) genes have been implicated in disease pathogenesis...
May 18, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28522681/endothelial-nox1-oxidase-assembly-in-human-pulmonary-arterial-hypertension-driver-of-gremlin1-mediated-proliferation
#3
Imad Al Ghouleh, Sanghamitra Sahoo, Daniel N Meijles, Jefferson H Amaral, Daniel S de Jesus, John Sembrat, Mauricio Rojas, Dmitry A Goncharov, Elena A Goncharova, Patrick J Pagano
Background: Pulmonary arterial hypertension (PAH) is a rapidly degenerating and devastating disease of increased pulmonary vessel resistance leading to right heart failure. Palliative modalities remain limited despite recent endeavors to investigate the mechanisms underlying increased pulmonary vascular resistance, i.e. aberrant vascular remodeling and occlusion. However, little is known of the molecular mechanisms responsible for endothelial proliferation, a root cause of PAH-associated vascular remodeling...
May 18, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28513431/dissection-of-zebrafish-shha-function-using-site-specific-targeting-with-a-cre-dependent-genetic-switch
#4
Kotaro Sugimoto, Subhra P Hui, Delicia Z Sheng, Kazu Kikuchi
Despite the extensive use of zebrafish as a model organism in developmental biology and regeneration research, genetic techniques enabling conditional analysis of gene function are limited. In this study, we generated Zwitch, a Cre-dependent invertible gene-trap cassette, enabling the establishment of conditional alleles in zebrafish by generating intronic insertions via in vivo homologous recombination. To demonstrate the utility of Zwitch, we generated a conditional sonic hedgehog a (shha) allele. Homozygous shha mutants developed normally; however, shha mutant embryos globally expressing Cre exhibited strong reductions in endogenous shha and shha target gene mRNA levels and developmental defects associated with null shha mutations...
May 17, 2017: ELife
https://www.readbyqxmd.com/read/28512846/melatonin-influences-the-sonic-hedgehog-signaling-pathway-in-porcine-cumulus-oocyte-complexes
#5
Sanghoon Lee, Jun-Xue Jin, Anukul Taweechaipaisankul, Geon A Kim, Curie Ahn, Byeong Chun Lee
Melatonin, which is synthesized in the pineal gland and peripheral reproductive organs, has antioxidant properties and regulates physiological processes. It is well known that melatonin affects in vitro maturation (IVM) of oocytes and embryonic development in many species. However, beneficial effects of melatonin on IVM have been explained mainly by indirect antioxidant effects and little information is available on the underlying mechanism by which melatonin directly acts on porcine cumulus oocyte complexes (COCs)...
May 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28507311/disruption-of-shh-signaling-cascade-by-sbe-attenuates-lung-cancer-progression-and-sensitizes-ddp-treatment
#6
Jing Du, Weiwei Chen, Lijuan Yang, Juanjuan Dai, Jiwei Guo, Yan Wu, Kaikai Gong, Jian Zhang, Ning Yu, Zhen Xie, Sichuan Xi
Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression, and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and renders a therapeutic interference option to lung cancer patients with poor prognosis. In this study, we screened and evaluated the specificity of a Chinese herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling pathway to block NSCLC progression. Our study confirmed that aberrant activation of the SHH signal pathway conferred more proliferative and invasive phenotypes to human lung cancer cells...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28506991/sonic-hedgehog-regulation-of-foxf2-promotes-cranial-neural-crest-mesenchyme-proliferation-and-is-disrupted-in-cleft-lip-morphogenesis
#7
Joshua L Everson, Dustin M Fink, Joon Won Yoon, Elizabeth J Leslie, Henry W Kietzman, Lydia J Ansen-Wilson, Hannah M Chung, David O Walterhouse, Mary L Marazita, Robert J Lipinski
Cleft lip is one of the most common human birth defects, yet our understanding of the mechanisms that regulate lip morphogenesis is limited. Here, we show that Sonic Hedgehog (Shh)-induced proliferation of cranial neural crest cell (cNCC) mesenchyme is required for upper lip closure. Gene expression profiling revealed a subset of Forkhead box (Fox) genes regulated by Shh signaling during lip morphogenesis. During cleft pathogenesis, reduced proliferation in the medial nasal process mesenchyme paralleled the domain of reduced Foxf2 and Gli1 expression...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28504423/genetic-vulnerabilities-to-prenatal-alcohol-exposure-limb-defects-in-sonic-hedgehog-and-gli2-heterozygous-mice
#8
Eric W Fish, Laura B Murdaugh, Kathleen K Sulik, Kevin P Williams, Scott E Parnell
BACKGROUND: Genetic factors influence the physical and neurobehavioral manifestations of prenatal alcohol exposure (PAE). Animal models allow the investigation of specific genes that confer vulnerability to, or protection from, birth defects associated with fetal alcohol spectrum disorders (FASDs). The objective of the present experiments was to determine if genetic alterations in the Sonic Hedgehog (Shh) signaling pathways affect the vulnerability to PAE-induced skeletal defects involving the forelimbs and/or hindlimbs...
May 15, 2017: Birth Defects Res
https://www.readbyqxmd.com/read/28496132/serum-sonic-hedgehog-shh-and-interleukin-il-6-as-dual-prognostic-biomarkers-in-progressive-metastatic-breast-cancer
#9
A S Noman, M Uddin, A A Chowdhury, M J Nayeem, Z Raihan, M I Rashid, A K Azad, M L Rahman, D Barua, A Sultana, A Shirin, J Ferdous, R R Parag, S M Rahman, M R Mahmud, C S Jerin, N Jahan, A Siddiqua, T Ara, E B Sabur, S S Alam, S Baidya, S Akther, M Z Rahman, T Banu, A K Murugan, S Sabri, S M S Islam, B Karakas, A Aboussekhra, H Yeger, W A Farhat, S S Islam
Serum from one hundred and ten breast cancer patients and thirty healthy female volunteers, were prospectively collected and evaluated for serum levels of Shh and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All patients were regularly monitored for event free survival (EFS) and overall survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels. In patients with progressive metastatic BC, both serum Shh and IL-6 concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients, respectively, at a statistically significant level [Shh (p = 0...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28493069/comparison-of-molecular-marker-expression-in-early-zebrafish-brain-development-following-chronic-ethanol-or-morpholino-treatment
#10
Chengjin Zhang, Oswald Boa-Amponsem, Gregory J Cole
This study was undertaken to ascertain whether defined markers of early zebrafish brain development are affected by chronic ethanol exposure or morpholino knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors, four signaling molecules that are suggested to be ethanol sensitive. Zebrafish embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha, aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early brain development...
May 10, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28490517/atoh1-promotes-leptomeningeal-dissemination-and-metastasis-of-sonic-hedgehog-subgroup-medulloblastomas
#11
Katie B Grausam, Samuel Dr Dooyema, Laure Bihannic, Hasitha Premathilake, A Sorana Morrissy, Antoine Forget, Amanda M Schaefer, Justin H Gundelach, Slobodan Macura, Diane M Maher, Xin Wang, Alex H Heglin, Xijin Ge, Erliang Zeng, Stephanie Puget, Indra Chandrasekar, Kameswaran Surendran, Richard J Bram, Ulrich Schüller, Michael D Taylor, Olivier Ayrault, Haotian Zhao
Medulloblastoma (MB) arising from the cerebellum is the most common pediatric brain malignancy, with leptomeningeal metastases often present at diagnosis and recurrence associated with poor clinical outcome. In this study, we employed mouse MB models to explore the relationship of tumor pathophysiology and dysregulated expression of the Notch pathway transcription factor ATOH1, which is present in aggressive MB subtypes driven by aberrant Sonic Hedgehog/Patched (SHH/PTCH) signaling. In experiments with conditional Atoh1 mouse mutants crossed to Ptch1(+/-) mice which develop SHH-driven MB[63], animals with Atoh1 transgene expression developed highly penetrant MB at a young age with extensive leptomeningeal disease and metastasis to the spinal cord and brain, resembling xenografts of human SHH MB...
May 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28490013/sulfatase-2-modulates-fate-change-from-motor-neurons-to-oligodendrocyte-precursor-cells-through-coordinated-regulation-of-shh-signaling-with-sulfatase-1
#12
Wen Jiang, Yugo Ishino, Hirokazu Hashimoto, Kazuko Keino-Masu, Masayuki Masu, Kenji Uchimura, Kenji Kadomatsu, Takeshi Yoshimura, Kazuhiro Ikenaka
Sulfatases (Sulfs) are a group of endosulfatases consisting of Sulf1 and Sulf2, which specifically remove sulfate from heparan sulfate proteoglycans. Although several studies have shown that Sulf1 acts as a regulator of sonic hedgehog (Shh) signaling during embryonic ventral spinal cord development, the detailed expression pattern and function of Sulf2 in the spinal cord remains to be determined. In this study, we found that Sulf2 also modulates the cell fate change from motor neurons (MNs) to oligodendrocyte precursor cells (OPCs) by regulating Shh signaling in the mouse ventral spinal cord in coordination with Sulf1...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28487338/poststroke-sonic-hedgehog-agonist-treatment-improves-functional-recovery-by-enhancing-neurogenesis-and-angiogenesis
#13
Yongming Jin, Austin Barnett, Yifan Zhang, Xin Yu, Yu Luo
BACKGROUND AND PURPOSE: Because of the limitation in treatment window of the r-tPA (recombinant tissue-type plasminogen activator), the development of delayed treatment for stroke is needed. In this study, we examined the efficacy of delayed poststroke treatment (post 3-8 days) of the sonic hedgehog pathway agonist on functional recovery and the underlying mechanisms. METHODS: We evaluated functional recovery at 1 month after stroke using locomotion analysis and Barnes maze test for cognitive function...
May 9, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28485896/shh-signalling-mediates-astrocyte-crosstalk-with-neurons-to-confer-neuroprotection
#14
Christopher I Ugbode, Imogen Smith, Benjamin J Whalley, Warren D Hirst, Marcus Rattray
Sonic Hedgehog (SHH) is a glycoprotein associated with development that is also expressed in the adult CNS and released after brain injury. Since the SHH receptors PTCH1 (patched homolog-1) and SMO (Smoothened) are highly expressed on astrocytes, we hypothesised that SHH regulates astrocyte function. Primary mouse cortical astrocytes derived from embryonic (E15) Swiss mouse cortices, were treated with two chemically distinct agonists of the SHH pathway, which caused astrocytes to elongate and proliferate. These changes are accompanied by decreases in the major astrocyte glutamate transporter, GLT-1 and the astrocyte intermediate filament protein GFAP...
May 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28477008/combination-therapy-with-micellarized-cyclopamine-and-temozolomide-attenuate-glioblastoma-growth-through-gli1-down-regulation
#15
Yu-Jie Liu, Ying-Cong Ma, Wen-Jie Zhang, Zhen-Zhen Yang, De-Sheng Liang, Zhi-Fu Wu, Xian-Rong Qi
Glioblastoma multiforme (GBM) is the most common and deadly brain cancer, characterized by its aggressive proliferation to adjacent tissue and high recurrence rate. We studied the efficacy and related mechanisms of the combination of cyclopamine (Cyp, a Sonic-hedgehog pathway (Shh) inhibitor) and temozolomide (TMZ, the clinically most used chemotherapeutic agent) in anti-GBM treatment. The micellarized Cyp (MCyp) showed better performance than Cyp solution in inhibiting GBM cells proliferation (3.77-fold against U87 MG cells and 3...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28473325/a-novel-role-for-primary-cilia-in-airway-remodeling
#16
Carol S Trempus, Weifeng Song, Ahmed Lazrak, Zhihong Yu, Judy R Creighton, Bethany M Young, Rebecca L Heise, Yen R Yu, Jennifer L Ingram, Robert M Tighe, Sadis Matalon, Stavros Garantziotis
Primary cilia (PC) are solitary cellular organelles that play critical roles in development, homeostasis, and disease pathogenesis by modulating key signaling pathways such as sonic hedgehog and calcium flux. The antenna-like shape of PC enables them also to facilitate sensing of extracellular and mechanical stimuli into the cell, and a critical role for PC has been described for mesenchymal cells such as chondrocytes. However, nothing is known about the role of PC in airway smooth muscle cells (ASMC) in the context of airway remodeling...
May 4, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28472290/changes-in-the-proliferative-program-limit-astrocyte-homeostasis-in-the-aged-post-traumatic-murine-cerebral-cortex
#17
Gábor Heimann, Luisa L Canhos, Jesica Frik, Gabriele Jäger, Tjasa Lepko, Jovica Ninkovic, Magdalena Götz, Swetlana Sirko
Aging leads to adverse outcomes after traumatic brain injury. The mechanisms underlying these defects, however, are not yet clear. In this study, we found that astrocytes in the aged post-traumatic cerebral cortex develop a significantly reduced proliferative response, resulting in reduced astrocyte numbers in the penumbra. Moreover, experiments of reactive astrocytes in vitro reveal that their diminished proliferation is due to an age-related switch in the division mode with reduced cell-cycle re-entry rather than changes in cell-cycle length...
May 4, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28469835/developing-an-ancient-epithelial-appendage-fgf-signalling-regulates-early-tail-denticle-formation-in-sharks
#18
Rory L Cooper, Kyle J Martin, Liam J Rasch, Gareth J Fraser
BACKGROUND: Vertebrate epithelial appendages constitute a diverse group of organs that includes integumentary structures such as reptilian scales, avian feathers and mammalian hair. Recent studies have provided new evidence for the homology of integumentary organ development throughout amniotes, despite their disparate final morphologies. These structures develop from conserved molecular signalling centres, known as epithelial placodes. It is not yet certain whether this homology extends beyond the integumentary organs of amniotes, as there is a lack of knowledge regarding their development in basal vertebrates...
2017: EvoDevo
https://www.readbyqxmd.com/read/28458545/role-of-hedgehog-gli1-signaling-in-the-enhanced-proliferation-and-differentiation-of-mg63-cells-enabled-by-hierarchical-micro-nanotextured-topography
#19
Yao Lin, Yinghe Huang, Junbing He, Feng Chen, Yanfang He, Wenying Zhang
Hedgehog-Gli1 signaling is evolutionarily conserved and plays an essential role in osteoblast proliferation and differentiation as well as bone formation. To evaluate the role of the Hedgehog-Gli1 pathway in the response of osteoblasts to hierarchical biomaterial topographies, human MG63 osteoblasts were seeded onto smooth, microstructured, and micro-/nanotextured topography (MNT) titanium to assess osteoblast proliferation and differentiation in terms of proliferative activity, alkaline phosphatase (ALP) production, and osteogenesis-related gene expression...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28448983/intrauterine-growth-restriction-alters-the-postnatal-development-of-the-rat-cerebellum
#20
Annie R A McDougall, Vanny Wiradjaja, Aminath Azhan, Anqi Li, Nadia Hale, Mary E Wlodek, Stuart B Hooper, Megan J Wallace, Mary Tolcos
Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0...
April 28, 2017: Developmental Neuroscience
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