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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 MUC4 resistant piglets for 1 week before the F4-expressing ETEC strain (F4(+) ETEC) challenge. The luminal contents were collected from the mucosa of colon on day 8 after F4(+) ETEC challenge. BLS-mix attenuated E. coli-induced expansion of Bacteroides uniformis, Eubacterium eligens, Acetanaerobacterium and Sporobacter populations...
November 23, 2016: Applied and Environmental Microbiology
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
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...
September 13, 2016: Journal of Cancer Research and Clinical Oncology
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
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
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
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
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
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
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 non-prosensory 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...
May 20, 2016: Developmental Neurobiology
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
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
Zlatka P Stojanova, Tao Kwan, Neil Segil
No abstract text is available yet for this article.
May 1, 2016: Development
Shuna Li, Wei Qian, Guochang Jiang, Yongming Ma
Inner ear hair cells are the sensory receptors that detect and convert sound vibrations and head movements into neural signals. However, in humans, these cells are unable to regenerate if they are damaged or lost. Over thepast decade,there has been an exponential increase in interest and progress in understanding of the development of the inner ear and of hair cells, aiming to gain insights into hair cell repair or even regeneration. In hair cell development, various transcription factors have been found to be involved in the processes of hair cell proliferation, differentiation and survival...
2016: Frontiers in Bioscience (Landmark Edition)
Nesrine Abboud, Arnaud Fontbonne, Isabelle Watabe, Alain Tonetto, Jean Michel Brezun, François Feron, Azel Zine
The generation of replacement inner ear hair cells (HCs) remains a challenge and stem cell therapy holds the potential for developing therapeutic solutions to hearing and balance disorders. Recent developments have made significant strides in producing mouse otic progenitors using cell culture techniques to initiate HC differentiation. However, no consensus has been reached as to efficiency and therefore current methods remain unsatisfactory. In order to address these issues, we compare the generation of otic and HC progenitors from embryonic stem (ES) cells in two cell culture systems: suspension vs...
April 21, 2016: Journal of Tissue Engineering and Regenerative Medicine
X Shi, Q Wang, J Gu, Z Xuan, J I Wu
Recent large-scale genomic studies have classified medulloblastoma into four subtypes: Wnt, Shh, Group 3 and Group 4. Each is characterized by specific mutations and distinct epigenetic states. Previously, we showed that a chromatin regulator SMARCA4/Brg1 is required for Gli-mediated transcription activation in Sonic hedgehog (Shh) signaling. We report here that Brg1 controls a transcriptional program that specifically regulates Shh-type medulloblastoma growth. Using a mouse model of Shh-type medulloblastoma, we deleted Brg1 in precancerous progenitors and primary or transplanted tumors...
April 11, 2016: Oncogene
Hans Gerd Nothwang
Localization of sound sources is a central aspect of auditory processing. A unique feature of mammals is the smooth, tonotopically organized extension of the hearing range to high frequencies (HF) above 10kHz, which likely induced positive selection for novel mechanisms of sound localization. How this change in the auditory periphery is accompanied by changes in the central auditory system is unresolved. I will argue that the major VGlut2(+) excitatory projection neurons of sound localization circuits (dorsal cochlear nucleus (DCN), lateral and medial superior olive (LSO and MSO)) represent serial homologs with modifications, thus being paramorphs...
June 2016: Progress in Neurobiology
Judith S Kempfle, Jack L Turban, Albert S B Edge
HMG domain transcription factor, Sox2, is a critical gene for the development of cochlear hair cells, the receptor cells for hearing, but this has been ascribed to expansion of the progenitors that become hair cells. Here, we show that Sox2 activated Atoh1, a transcription factor important for hair cell differentiation, through an interaction with the 3' enhancer of Atoh1. Binding to consensus sequences in the Atoh1 enhancer was dependent on the level of Sox2, and the extent of enhancer binding correlated to the extent of activation...
2016: Scientific Reports
Yassan Abdolazimi, Zlatka Stojanova, Neil Segil
Determination of cell fate within the prosensory domain of the developing cochlear duct relies on the temporal and spatial regulation of the bHLH transcription factor Atoh1. Auditory hair cells and supporting cells arise in a wave of differentiation that patterns them into discrete rows mediated by Notch-dependent lateral inhibition. However, the mechanism responsible for selecting sensory cells from within the prosensory competence domain remains poorly understood. We show in mice that rather than being upregulated in rows of cells, Atoh1 is subject to transcriptional activation in groups of prosensory cells, and that highly conserved sites for Hes/Hey repressor binding in the Atoh1 promoter are needed to select the hair cell and supporting cell fate...
March 1, 2016: Development
Ryohei Hayashi, Kiichiro Tsuchiya, Keita Fukushima, Nobukatsu Horita, Shuji Hibiya, Keisuke Kitagaki, Mariko Negi, Eisaku Itoh, Takumi Akashi, Yoshinobu Eishi, Eriko Okada, Akihiro Araki, Kazuo Ohtsuka, Shinji Fukuda, Hiroshi Ohno, Ryuichi Okamoto, Tetsuya Nakamura, Shinji Tanaka, Kazuaki Chayama, Mamoru Watanabe
BACKGROUND: Mucosal barrier dysfunction is considered a critical component of Crohn's disease (CD) pathogenesis after the identification of susceptibility genes. However, the precise mechanism underlying mucosal barrier dysfunction has not yet been elucidated. We therefore aimed to elucidate the molecular mechanism underlying the expression of human α-defensin 6 (HD6) in patients with CD. METHODS: HD6 expression was induced by the transfection of an atonal homolog 1 (Atoh1) transgene and was assessed by reverse transcription polymerase chain reaction...
May 2016: Inflammatory Bowel Diseases
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