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https://www.readbyqxmd.com/read/28184337/atoh1-as-a-coordinator-of-sensory-hair-cell-development-and-regeneration-in-the-cochlea
#1
Sungsu Lee, Han-Seong Jeong, Hyong-Ho Cho
Cochlear sensory hair cells (HCs) are crucial for hearing as mechanoreceptors of the auditory systems. Clarification of transcriptional regulation for the cochlear sensory HC development is crucial for the improvement of cell replacement therapies for hearing loss. Transcription factor Atoh1 is the key player during HC development and regeneration. In this review, we will focus on Atoh1 and its related signaling pathways (Notch, fibroblast growth factor, and Wnt/β-catenin signaling) involved in the development of cochlear sensory HCs...
January 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/28174757/transcriptional-regulation-by-atoh1-and-its-target-spdef-in%C3%A2-the%C3%A2-intestine
#2
Yuan-Hung Lo, Eunah Chung, Zhaohui Li, Ying-Wooi Wan, Maxime M Mahe, Min-Shan Chen, Taeko K Noah, Kristin N Bell, Hari Krishna Yalamanchili, Tiemo J Klisch, Zhandong Liu, Joo-Seop Park, Noah F Shroyer
BACKGROUND & AIMS: The transcription factor atonal homolog 1 (ATOH1) controls the fate of intestinal progenitors downstream of the Notch signaling pathway. Intestinal progenitors that escape Notch activation express high levels of ATOH1 and commit to a secretory lineage fate, implicating ATOH1 as a gatekeeper for differentiation of intestinal epithelial cells. Although some transcription factors downstream of ATOH1, such as SPDEF, have been identified to specify differentiation and maturation of specific cell types, the bona fide transcriptional targets of ATOH1 still largely are unknown...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#3
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28052248/hox2-genes-are-required-for-tonotopic-map-precision-and-sound-discrimination-in-the-mouse-auditory-brainstem
#4
Kajari Karmakar, Yuichi Narita, Jonathan Fadok, Sebastien Ducret, Alberto Loche, Taro Kitazawa, Christel Genoud, Thomas Di Meglio, Raphael Thierry, Joao Bacelo, Andreas Lüthi, Filippo M Rijli
Tonotopy is a hallmark of auditory pathways and provides the basis for sound discrimination. Little is known about the involvement of transcription factors in brainstem cochlear neurons orchestrating the tonotopic precision of pre-synaptic input. We found that in the absence of Hoxa2 and Hoxb2 function in Atoh1-derived glutamatergic bushy cells of the anterior ventral cochlear nucleus, broad input topography and sound transmission were largely preserved. However, fine-scale synaptic refinement and sharpening of isofrequency bands of cochlear neuron activation upon pure tone stimulation were impaired in Hox2 mutants, resulting in defective sound-frequency discrimination in behavioral tests...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28044390/systematic-in-vitro-and-in-vivo-characterization-of-leukemia-inhibiting-factor-and-fibroblast-growth-factor-derived-porcine-induced-pluripotent-stem-cells
#5
Jan O Secher, Ahmet Ceylan, Gianluca Mazzoni, Kaveh Mashayekhi, Tong Li, Suchitra Muenthaisong, Troels T Nielsen, Dong Li, Shengting Li, Stoyan Petkov, Susanna Cirera, Yonglun Luo, Lori Thombs, Haja N Kadarmideen, Andras Dinnyes, Lars Bolund, Bernard A J Roelen, Mette Schmidt, Henrik Callesen, Poul Hyttel, Kristine K Freude
Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to shed more light on the underlying biological mechanisms of porcine pluripotency. LIF-derived piPSCs were more successful than their FGF-derived counterparts in the generation of in vitro chimeras and in teratoma formation...
January 3, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28030585/organ-of-corti-and-stria-vascularis-is-there-an-interdependence-for-survival
#6
Huizhan Liu, Yi Li, Lei Chen, Qian Zhang, Ning Pan, David H Nichols, Weiping J Zhang, Bernd Fritzsch, David Z Z He
Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria...
2016: PloS One
https://www.readbyqxmd.com/read/28025176/beyond-proneural-emerging-functions-and-regulations-of-proneural-proteins
#7
REVIEW
François Guillemot, Bassem A Hassan
Proneural proteins, which include Ascl1, Atoh1 and Neurogenins épinière in vertebrates and Achaete-Scute proteins and Atonal in Drosophila, are expressed in the developing nervous system throughout the animal kingdom and have an essential and well-characterised role in specifying the neural identity of progenitors. New properties and additional roles of these factors have emerged in recent years, including the regulation of stem cell proliferation and the capacity to reprogram many types of cells into neurons...
December 22, 2016: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/27881419/oral-administration-of-a-select-mixture-of-bacillus-probiotics-affects-the-gut-microbiota-and-goblet-cell-function-following-escherichia-coli-challenge-in-newly-weaned-pigs-of-genotype-muc4-that-are-supposed-to-be-enterotoxigenic-e-coli-f4ab-ac-receptor-negative
#8
Wei Zhang, Yao-Hong Zhu, Dong Zhou, Qiong Wu, Dan Song, Johan Dicksved, Jiu-Feng Wang
: Structural disruption of the gut microbiota and impaired goblet cell function are collateral etiologic factors in enteric diseases. Low, moderate, or high doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally administered to piglets of genotype MUC4 that are supposed to be F4-expressing enterotoxigenic Escherichia coli strain (F4(+) ETEC) F4ab/ac receptor negative (i.e., MUC4-resistant piglets) for 1 week before F4(+) ETEC challenge. The luminal contents were collected from the mucosa of the colon on day 8 after F4(+) ETEC challenge...
February 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27751776/atoh1-in-sensory-hair-cell-development-constraints-and-cofactors
#9
Aida Costa, Lynn M Powell, Sally Lowell, Andrew P Jarman
The proneural gene, Atoh1, is necessary and in some contexts sufficient for early inner ear hair cell development. Its function is the subject of intensive research, not least because of the possibility that it could be used in therapeutic strategies to reverse hair cell loss in deafness. However, it is clear that Atoh1's function is highly context dependent. During inner ear development, Atoh1 is only able to promote hair cell differentiation at specific developmental stages. Outside the ear, Atoh1 is required for differentiation of a variety of other cell types, for example in the intestine and cerebellum...
October 14, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27624714/prognostic-relevance-of-high-atonal-homolog-1-expression-in-merkel-cell-carcinoma
#10
T Gambichler, S Mohtezebsade, U Wieland, S Silling, A-K Höh, M Dreißigacker, J Schaller, H-J Schulze, F Oellig, A Kreuter, E Stockfleth, M Stücker, F G Bechara, J C Becker
BACKGROUND: It has recently been reported that atonal homolog 1 (ATOH1) gene is down-regulated in Merkel cell carcinoma (MCC) and thus may represent a tumor suppressor gene. OBJECTIVES: We aimed to test for ATOH1 gene mutations and expression levels in MCC tissues and cell lines. METHODS: Genomic DNA isolation and amplification via PCR was successfully performed in 33 MCCs on formalin-fixed paraffin-embedded tissue and three MCC cell lines, followed by Sanger sequencing of the whole ATOH1 gene to detect genomic aberrations...
January 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27576864/dissecting-the-pre-placodal-transcriptome-to-reveal-presumptive-direct-targets-of-six1-and-eya1-in-cranial-placodes
#11
Nick Riddiford, Gerhard Schlosser
The pre-placodal ectoderm, marked by the expression of the transcription factor Six1 and its co-activator Eya1, develops into placodes and ultimately into many cranial sensory organs and ganglia. Using RNA-Seq in Xenopus laevis we screened for presumptive direct placodal target genes of Six1 and Eya1 by overexpressing hormone-inducible constructs of Six1 and Eya1 in pre-placodal explants, and blocking protein synthesis before hormone-inducing nuclear translocation of Six1 or Eya1. Comparing the transcriptome of explants with non-induced controls, we identified hundreds of novel Six1/Eya1 target genes with potentially important roles for placode development...
August 31, 2016: ELife
https://www.readbyqxmd.com/read/27559308/lgr4-and-lgr5-regulate-hair-cell-differentiation-in-the-sensory-epithelium-of-the-developing-mouse-cochlea
#12
Magdalena Żak, Thijs van Oort, Ferry G Hendriksen, Marie-Isabelle Garcia, Gilbert Vassart, Wilko Grolman
In the developing cochlea, Wnt/β-catenin signaling positively regulates the proliferation of precursors and promotes the formation of hair cells by up-regulating Atoh1 expression. Not much, however, is known about the regulation of Wnt/β-catenin activity in the cochlea. In multiple tissues, the activity of Wnt/β-catenin signaling is modulated by an interaction between LGR receptors and their ligands from the R-spondin family. The deficiency in Lgr4 and Lgr5 genes leads to developmental malformations and lethality...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27542412/destabilization-of-atoh1-by-e3-ubiquitin-ligase-huwe1-and-casein-kinase-1-is-essential-for-normal-sensory-hair-cell-development
#13
Yen-Fu Cheng, Mingjie Tong, Albert S B Edge
Proneural basic helix-loop-helix transcription factor, Atoh1, plays a key role in the development of sensory hair cells. We show here that the level of Atoh1 must be accurately controlled by degradation of the protein in addition to the regulation of Atoh1 gene expression to achieve normal cellular patterning during development of the cochlear sensory epithelium. The stability of Atoh1 was regulated by the ubiquitin proteasome system through the action of Huwe1, a HECT-domain, E3 ubiquitin ligase. An interaction between Huwe1 and Atoh1 could be visualized by a proximity ligation assay and was confirmed by co-immunoprecipitation and mass spectrometry...
September 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27535918/extensive-supporting-cell-proliferation-and-mitotic-hair-cell-generation-by-in-vivo-genetic-reprogramming-in-the-neonatal-mouse-cochlea
#14
Wenli Ni, Chen Lin, Luo Guo, Jingfang Wu, Yan Chen, Renjie Chai, Wenyan Li, Huawei Li
UNLABELLED: The generation of hair cells (HCs) from the differentiation of proliferating supporting cells (SCs) appears to be an ideal approach for replacing lost HCs in the cochlea and is promising for restoring hearing after damage to the organ of Corti. We show here that extensive proliferation of SCs followed by mitotic HC generation is achieved through a genetic reprogramming process involving the activation of β-catenin to upregulate Wnt signaling, the deletion of Notch1 to downregulate Notch signaling, and the overexpression of Atoh1 in Sox2(+) SCs in neonatal mouse cochleae...
August 17, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27527363/role-of-wnt-and-notch-signaling-in-regulating-hair-cell-regeneration-in-the-cochlea
#15
REVIEW
Muhammad Waqas, Shasha Zhang, Zuhong He, Mingliang Tang, Renjie Chai
Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells...
September 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27431290/clinical-genomics-expands-the-morbid-genome-of-intellectual-disability-and-offers-a-high-diagnostic-yield
#16
S Anazi, S Maddirevula, E Faqeih, H Alsedairy, F Alzahrani, H E Shamseldin, N Patel, M Hashem, N Ibrahim, F Abdulwahab, N Ewida, H S Alsaif, H Al Sharif, W Alamoudi, A Kentab, F A Bashiri, M Alnaser, A H AlWadei, M Alfadhel, W Eyaid, A Hashem, A Al Asmari, M M Saleh, A AlSaman, K A Alhasan, M Alsughayir, M Al Shammari, A Mahmoud, Z N Al-Hassnan, M Al-Husain, R Osama Khalil, N Abd El Meguid, A Masri, R Ali, T Ben-Omran, P El Fishway, A Hashish, A Ercan Sencicek, M State, A M Alazami, M A Salih, N Altassan, S T Arold, M Abouelhoda, S M Wakil, D Monies, R Shaheen, F S Alkuraya
Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196)...
July 19, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27203669/dual-role-for-sox2-in-specification-of-sensory-competence-and-regulation-of-atoh1-function
#17
Chandrakala Puligilla, Matthew W Kelley
The formation of inner ear sensory epithelia is believed to occur in two steps, initial specification of sensory competent (prosensory) regions followed by determination of specific cell-types, such as hair cells (HCs) and supporting cells. However, studies in which the HC determination factor Atoh1 was ectopically expressed in nonprosensory regions indicated that expression of Atoh1 alone is sufficient to induce HC formation suggesting that prosensory formation may not be a prerequisite for HC development...
January 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/27189205/regeneration-of-hair-cells-in-the-mammalian-vestibular-system
#18
REVIEW
Wenyan Li, Dan You, Yan Chen, Renjie Chai, Huawei Li
Hair cells regenerate throughout the lifetime of non-mammalian vertebrates, allowing these animals to recover from hearing and balance deficits. Such regeneration does not occur efficiently in humans and other mammals. Thus, balance deficits become permanent and is a common sensory disorder all over the world. Since Forge and Warchol discovered the limited spontaneous regeneration of vestibular hair cells after gentamicininduced damage in mature mammals, significant efforts have been exerted to trace the origin of the limited vestibular regeneration in mammals after hair cell loss...
June 2016: Frontiers of Medicine
https://www.readbyqxmd.com/read/27158355/dapt-mediates-atoh1-expression-to-induce-hair-cell-like-cells
#19
Hongmiao Ren, Weiwei Guo, Wei Liu, Weiqiang Gao, Dinghua Xie, Tuanfang Yin, Shiming Yang, Jihao Ren
Hearing loss is currently an incurable degenerative disease characterized by a paucity of hair cells (HCs), which cannot be spontaneously replaced in mammals. Recent technological advancements in gene therapy and local drug delivery have shed new light for hearing loss. Atoh1, also known as Math1, Hath1, and Cath1, is a proneural basic helix-loop-helix (bHLH) transcription factor that is essential for HC differentiation. At various stages in development, Atoh1 activity is sufficient to drive HC differentiation in the cochlea...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27143757/epigenetic-regulation-of-atoh1-guides-hair-cell-development-in-the-mammalian-cochlea
#20
Zlatka P Stojanova, Tao Kwan, Neil Segil
No abstract text is available yet for this article.
May 1, 2016: Development
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