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Sonic hedgehog

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https://www.readbyqxmd.com/read/28807898/hypothalamic-sonic-hedgehog-is-required-for-cell-specification-and-proliferation-of-lhx3-lhx4-pituitary-embryonic-precursors
#1
G Carreno, J Apps, E J Lodge, L Panousopoulos, S Haston, J M Gonzalez-Meljem, H Hahn, C L Andoniadou, J P Martinez-Barbera
Sonic hedgehog (SHH) is an essential morphogenetic signal dictating cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead, a critical role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28807161/phytochemical-modulation-of-apoptosis-and-autophagy-strategies-to-overcome-chemoresistance-in-leukemic-stem-cells-in-the-bone-marrow-microenvironment
#2
Helen C Owen, Sandra Appiah, Noor Hasan, Lucy Ghali, Ghada Elayat, Celia Bell
Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as "sanctuaries" where LSCs acquire drug resistance...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28799057/expression-patterns-of-key-sonic-hedgehog-signaling-pathway-components-in-the-developing-and-adult-mouse-midbrain-and-in-the-mn9d-cell-line
#3
Melanie Feuerstein, Enaam Chleilat, Shokoufeh Khakipoor, Konstantinos Michailidis, Christian Ophoven, Eleni Roussa
The temporal dynamic expression of Sonic Hedgehog (SHH) and signaling during early midbrain dopaminergic (mDA) neuron development is one of the key players in establishing mDA progenitor diversity. However, whether SHH signaling is also required during later developmental stages and in mature mDA neurons is less understood. We study the expression of SHH receptors Ptch1 and Gas1 (growth arrest-specific 1) and of the transcription factors Gli1, Gli2 and Gli3 in mouse midbrain during embryonic development [embryonic day (E) 12...
August 11, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28798218/imaging-biomarkers-for-adult-medulloblastomas-genetic-entities-may-be-identified-by-their-mr-imaging-radiophenotype
#4
V C Keil, M Warmuth-Metz, C Reh, S J Enkirch, C Reinert, D Beier, D T W Jones, T Pietsch, H H Schild, E Hattingen, P Hau
BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas. MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists...
August 10, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28797033/a-shh-foxf1-bmp4-signaling-axis-regulating-growth-and-differentiation-of-epithelial-and-mesenchymal-tissues-in-ureter-development
#5
Tobias Bohnenpoll, Anna B Wittern, Tamrat M Mamo, Anna-Carina Weiss, Carsten Rudat, Marc-Jens Kleppa, Karin Schuster-Gossler, Irina Wojahn, Timo H-W Lüdtke, Mark-Oliver Trowe, Andreas Kispert
The differentiated cell types of the epithelial and mesenchymal tissue compartments of the mature ureter of the mouse arise in a precise temporal and spatial sequence from uncommitted precursor cells of the distal ureteric bud epithelium and its surrounding mesenchyme. Previous genetic efforts identified a member of the Hedgehog (HH) family of secreted proteins, Sonic hedgehog (SHH) as a crucial epithelial signal for growth and differentiation of the ureteric mesenchyme. Here, we used conditional loss- and gain-of-function experiments of the unique HH signal transducer Smoothened (SMO) to further characterize the cellular functions and unravel the effector genes of HH signaling in ureter development...
August 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28794168/notch-signaling-in-development-tissue-homeostasis-and-disease
#6
REVIEW
Chris Siebel, Urban Lendahl
Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body...
October 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28793263/the-conserved-sonic-hedgehog-limb-enhancer-consists-of-discrete-functional-elements-that-regulate-precise-spatial-expression
#7
Laura A Lettice, Paul Devenney, Carlo De Angelis, Robert E Hill
Expression of sonic hedgehog (Shh) in the limb bud is regulated by an enhancer called the zone of polarizing activity regulatory sequence (ZRS), which, in evolution, belongs to an ancient group of highly conserved cis regulators found in all classes of vertebrates. Here, we examined the endogenous ZRS in mice, using genome editing to establish the relationship between enhancer composition and embryonic phenotype. We show that enhancer activity is a consolidation of distinct activity domains. Spatial restriction of Shh expression is mediated by a discrete repressor module, whereas levels of gene expression are controlled by large overlapping domains containing varying numbers of HOXD binding sites...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28793255/%C3%AE-e-catenin-is-a-positive-regulator-of-pancreatic-islet-cell-lineage-differentiation
#8
Antonio J Jimenez-Caliani, Rudolf Pillich, Wendy Yang, Giuseppe R Diaferia, Paolo Meda, Laura Crisa, Vincenzo Cirulli
The development and function of epithelia depend on the establishment and maintenance of cell-cell adhesion and intercellular junctions, which operate as mechanosensor hubs for the transduction of biochemical signals regulating cell proliferation, differentiation, survival, and regeneration. Here, we show that αE-catenin, a key component of adherens junctions, functions as a positive regulator of pancreatic islet cell lineage differentiation by repressing the sonic hedgehog pathway (SHH). Thus, deletion of αE-catenin in multipotent pancreatic progenitors resulted in (1) loss of adherens junctions, (2) constitutive activation of SHH, (3) decrease in islet cell lineage differentiation, and (4) accumulation of immature Sox9(+) progenitors...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28782908/ectodysplasin-a-regulates-epithelial-barrier-function-through-sonic-hedgehog-signalling-pathway
#9
Sanming Li, Jing Zhou, Liying Zhang, Juan Li, Jingwen Yu, Ke Ning, Yangluowa Qu, Hui He, Yongxiong Chen, Peter S Reinach, Chia-Yang Liu, Zuguo Liu, Wei Li
Ectodysplasin A (Eda), a member of the tumour necrosis factor superfamily, plays an important role in ectodermal organ development. An EDA mutation underlies the most common of ectodermal dysplasias, that is X-linked hypohidrotic ectodermal dysplasia (XLHED) in humans. Even though it lacks a developmental function, the role of Eda during the postnatal stage remains elusive. In this study, we found tight junctional proteins ZO-1 and claudin-1 expression is largely reduced in epidermal, corneal and lung epithelia in Eda mutant Tabby mice at different postnatal ages...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28781964/loss-of-suppressor-of-fused-in-mid-corticogenesis-leads-to-the-expansion-of-intermediate-progenitors
#10
Odessa R Yabut, Hui Xuan Ng, Gloria Fernandez, Keejung Yoon, Jeremy Kuhn, Samuel J Pleasure
Neural progenitors in the embryonic neocortex must be tightly regulated in order to generate the correct number and projection neuron subtypes necessary for the formation of functional neocortical circuits. In this study, we show that the intracellular protein Suppressor of Fused (Sufu) regulates the proliferation of intermediate progenitor (IP) cells at later stages of corticogenesis to affect the number of Cux1+ upper layer neurons in the postnatal neocortex. This correlates with abnormal levels of the repressor form of Gli3 (Gli3R) and the ectopic expression of Patched 1 (Ptch1), a Sonic Hedgehog (Shh) target gene...
December 2016: Journal of Developmental Biology
https://www.readbyqxmd.com/read/28778067/exome-sequencing-analysis-of-murine-medulloblastoma-models-identifies-wdr11-as-a-potential-tumor-suppressor-in-group-3-tumors
#11
Lei Wei, Brian L Murphy, Gang Wu, Matthew Parker, John Easton, Richard J Gilbertson, Jinghui Zhang, Martine F Roussel
Mouse models of human cancers are widely used in cancer research, yet questions frequently arise regarding their faithfulness in recapitulating their human counterparts. To compare the somatic mutations of murine models with human medulloblastoma (MB), we performed whole-exome sequencing on 12 tumors representing three distinct medulloblastoma subgroups: Wnt, Sonic Hedgehog (Shh) and Group 3 (G3). In total, 64 somatic mutations were identified and validated, including 40 predicted to cause amino acid changes...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28771384/vax1-plays-an-indirect-role-in-the-etiology-of-murine-cleft-palate
#12
F Geoghegan, G M Xavier, A A Birjandi, M Seppala, M T Cobourne
Cleft lip with or without palate (CLP) and isolated cleft palate (CP) are common human developmental malformations with a complex etiology that reflects a failure of normal facial development. VAX1 encodes a homeobox-containing transcription factor identified as a candidate gene for CLP in human populations, with targeted deletion in mice associated with multiple anomalies, including disruption of the visual apparatus and basal forebrain, lobar holoprosencephaly, and CP. We have investigated Vax1 function during murine palatogenesis but found no evidence for a direct role in this process...
August 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28765042/mir-342-3p-elevates-osteogenic-differentiation-of-umbilical-cord-mesenchymal-stem-cells-via-inhibiting-sufu-in%C3%A2-vitro
#13
Mengqi Huang, Ying Qing, Qi Shi, Yingguang Cao, Ke Song
Human umbilical mesenchymal stem cells (UCMSCs) have been wildly used in tissue engineering field as a promising source because of their unlimited and noninvasive origin. To selectively induce osteogenic differentiation of UCMSCs, it's imperative to understand the regulatory molecular mechanism underlying the process of how these cells switch into osteogenic lineage path. We previously showed enhanced sonic hedgehog (Shh) signaling pathway upon osteogenic induction in mesenchymal stem cells. In this study, miRNA-seq analysis revealed substantial Shh-dependent expression of distinct miRNAs, including miR-342-3p, during ostogenesis...
July 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28759213/design-and-evolution-of-a-macrocyclic-peptide-inhibitor-of-the-sonic-hedgehog-patched-interaction
#14
Andrew E Owens, Ivan de Paola, William A Hansen, Yi-Wen Liu, Sagar D Khare, Rudi Fasan
The Hedgehog (Hh) signaling pathway plays a central role during embryonic development and its aber-rant activation has been implicated in the development and progression of several human cancers. Ma-jor efforts toward the identification of chemical modulators of the Hedgehog pathway has yielded sev-eral antagonists of the GPCR-like Smoothened receptor. In contrast, potent inhibitors of the Sonic Hedgehog/Patched interaction, the most upstream event in ligand-induced activation of this signaling pathway, have been elusive...
July 31, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28754612/differentiation-potential-of-human-cd133-positive-hematopoietic-stem-cells-into-motor-neuron-like-cells-in-vitro
#15
Sepideh Alavi Moghaddam, Behnam Yousefi, Davood Sanooghi, Faezeh Faghihi, Nasim Hayati Roodbari, Nikoo Bana, Mohammad Taghi Joghataei, Paria Pooyan, Babak Arjmand
Spinal cord injuries and motor neuron-related disorders impact on life of many patients around the world. Since pharmacotherapy and surgical approaches were not efficient to regenerate these types of defects; stem cell therapy as a good strategy to restore the lost cells has become the focus of interest among the scientists. Umbilical cord blood CD133(+) hematopoietic stem cells (UCB- CD133(+) HSCs) with self- renewal property and neural lineage differentiation capacity are ethically approved cell candidate for use in regenerative medicine...
July 25, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28751784/rapid-generation-of-opc-like-cells-from-human-pluripotent-stem-cells-for-treating-spinal-cord-injury
#16
Dae-Sung Kim, Se Jung Jung, Jae Souk Lee, Bo Young Lim, Hyun Ah Kim, Jeong-Eun Yoo, Dong-Wook Kim, Joong Woo Leem
Remyelination via the transplantation of oligodendrocyte precursor cells (OPCs) has been considered as a strategy to improve the locomotor deficits caused by traumatic spinal cord injury (SCI). To date, enormous efforts have been made to derive OPCs from human pluripotent stem cells (hPSCs), and significant progress in the transplantation of such cells in SCI animal models has been reported. The current methods generally require a long period of time (>2 months) to obtain transplantable OPCs, which hampers their clinical utility for patients with SCI...
July 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28745929/molecular-and-cellular-mechanisms-of-palate-development
#17
C Li, Y Lan, R Jiang
Development of the mammalian secondary palate involves highly dynamic morphogenetic processes, including outgrowth of palatal shelves from the oral side of the embryonic maxillary prominences, elevation of the initially vertically oriented palatal shelves to the horizontal position above the embryonic tongue, and subsequently adhesion and fusion of the paired palatal shelves at the midline to separate the oral cavity from the nasal cavity. Perturbation of any of these processes could cause cleft palate, a common birth defect that significantly affects patients' quality of life even after surgical treatment...
April 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28743797/sonic-hedgehog-from-both-nerves-and-epithelium-is-a-key-trophic-factor-for-taste-bud-maintenance
#18
David Castillo-Azofeifa, Justin T Losacco, Ernesto Salcedo, Erin J Golden, Thomas E Finger, Linda A Barlow
The integrity of taste buds is intimately dependent on an intact gustatory innervation, yet the molecular nature of this dependency is unknown. Here we show differentiation of new taste bud cells, but not progenitor proliferation, is interrupted in mice treated with a Hedgehog (Hh) pathway inhibitor (HPI), and that gustatory nerves are a source of Shh for taste bud renewal. Additionally, epithelial taste precursor cells express Shh transiently, and are a local supply of Hh ligand supporting taste cell renewal...
July 25, 2017: Development
https://www.readbyqxmd.com/read/28743502/cell-autonomous-sonic-hedgehog-signaling-contributes-to-maintenance-of-retinal-endothelial-tight-junctions
#19
Monica Diaz-Coranguez, Daniel L Chao, Enrique L Salero, Jeffrey L Goldberg, David A Antonetti
No abstract text is available yet for this article.
July 22, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28739739/transcriptional-profiling-of-sonic-hedgehog-in-a-prospective-cohort-of-breast-cancer-in-a-pakistani-population
#20
Syeda Kiran Riaz, Lin Ye, Namood E Sahar, Durkhshan Aman, Javeria Qadir, Jahangir Sarwar Khan, Muhammad Saeed, Wen G Jiang, Muhammad Faraz Arshad Malik
BACKGROUND/AIM: Constitutive activation of Sonic hedgehog (SHH) has been observed in different types of cancers. In the present study, expressional profiling of SHH in a breast cancer cohort (n=150) of a Pakistani population and its association with different molecular subtypes have been explored. MATERIALS AND METHODS: qRT-PCR and IHC were performed for expression analysis of SHH and its association with ER, PR, HER2 and Ki-67 were also statistically analyzed. RESULTS: A significant over-expression of SHH was observed in tumor tissues in comparison to their respective controls (p<0...
August 2017: Anticancer Research
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