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https://www.readbyqxmd.com/read/29902110/celastrol-enhances-atoh1-expression-in-inner-ear-stem-cells-and-promotes-their-differentiation-into-functional-auditory-neuronal-like-cells
#1
Zhao Han, Yu-Yan Gu, Ning Cong, Rui Ma, Fang-Lu Chi
We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation...
June 14, 2018: Organogenesis
https://www.readbyqxmd.com/read/29846597/insights-into-electroreceptor-development-and-evolution-from-molecular-comparisons-with-hair-cells
#2
Clare V H Baker, Melinda S Modrell
The vertebrate lateral line system comprises a mechanosensory division, with neuromasts containing hair cells that detect local water movement ("distant touch"); and an electrosensory division, with electrosensory organs that detect the weak, low-frequency electric fields surrounding other animals in water (primarily used for hunting). The entire lateral line system was lost in the amniote lineage with the transition to fully terrestrial life; the electrosensory division was lost independently in several lineages, including the ancestors of frogs and of teleost fishes...
May 29, 2018: Integrative and Comparative Biology
https://www.readbyqxmd.com/read/29786668/scf-c-kit-signaling-increased-mucin2-production-by-maintaining-atoh1-expression-in-mucinous-colorectal-adenocarcinoma
#3
Ping Shen, Shu Yang, Haimei Sun, Guilan Li, Bo Wu, Fengqing Ji, Tingyi Sun, Deshan Zhou
Mucinous colorectal adenocarcinoma (MCA) patients often a show high risk of malignant potential and a poorer survival rate. Given that the pathological feature and oncobiological characteristics of MCA are correlated with its abundant extracellular mucin2 (MUC2), we paid interest toward investigating the key factor that promotes MUC2 production exposure to highly-activated stem cell factor (SCF)/c-KIT signaling, which we believed to contribute to MCA formation. Long-term azoxymethane and dextran sodium sulfate treatment successfully induced MCA only in wild-type (WT) mice at week 37 and 43, while all c-kit loss-of-function mutant mice (Wadsm/m ) developed non-MCA...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29780306/spontaneous-hair-cell-regeneration-is-prevented-by-increased-notch-signaling-in-supporting-cells
#4
Melissa M McGovern, Luyi Zhou, Michelle R Randle, Brandon C Cox
During embryonic development, differentiation of cochlear progenitor cells into hair cells (HCs) or supporting cells (SCs) is partially controlled through Notch signaling. Many studies have shown that inhibition of Notch signaling allows SCs to convert into HCs in both normal and drug damaged neonatal mouse cochleae. This mechanism is also implicated during HC regeneration in non-mammalian vertebrates; however, the mechanism of spontaneous HC regeneration in the neonatal mouse cochlea is less understood. While inhibition of Notch signaling can force SCs to convert into HCs and increase the number of regenerated HCs, it is currently unknown whether this pathway is involved in spontaneous HC regeneration observed in vivo ...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29772246/preterm-birth-disrupts-cerebellar-development-by-affecting-granule-cell-proliferation-program-and-bergmann-glia
#5
Igor Y Iskusnykh, Randal K Buddington, Victor V Chizhikov
Preterm birth is a leading cause of long-term motor and cognitive deficits. Clinical studies suggest that some of these deficits result from disruption of cerebellar development, but the mechanisms that mediate cerebellar abnormalities in preterm infants are largely unknown. Furthermore, it remains unclear whether preterm birth and precocious exposure to the ex-utero environment directly disrupt cerebellar development or indirectly by increasing the probability of cerebellar injury, including that resulting from clinical interventions and protocols associated with the care of preterm infants...
May 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29770645/atoh1-regulation-in-the-cochlea-more-than-just-transcription
#6
REVIEW
Yen-Fu Cheng
More than 80% of all cases of deafness are related to the death or degeneration of cochlear hair cells and the associated spiral ganglion neurons, and a lack of regeneration of these cells leads to permanent hearing loss. Therefore, the regeneration of lost hair cells is an important goal for the treatment of deafness. Atoh1 is a basic helix-loop-helix (bHLH) transcription factor that is critical in both the development and regeneration of cochlear hair cells. Atoh1 is transcriptionally regulated by several signaling pathways, including Notch and Wnt signalings...
July 13, 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29754876/bone-morphogenetic-protein-4-antagonizes-hair-cell-regeneration-in-the-avian-auditory-epithelium
#7
Rebecca M Lewis, Jesse J Keller, Liangcai Wan, Jennifer S Stone
Permanent hearing loss is often a result of damage to cochlear hair cells, which mammals are unable to regenerate. Non-mammalian vertebrates such as birds replace damaged hair cells and restore hearing function, but mechanisms controlling regeneration are not understood. The secreted protein bone morphogenetic protein 4 (BMP4) regulates inner ear morphogenesis and hair cell development. To investigate mechanisms controlling hair cell regeneration in birds, we examined expression and function of BMP4 in the auditory epithelia (basilar papillae) of chickens of either sex after hair cell destruction by ototoxic antibiotics...
May 2, 2018: Hearing Research
https://www.readbyqxmd.com/read/29752714/post-crossing-segment-of-di1-commissural-axons-forms-collateral-branches-to-motor-neurons-in-the-developing-spinal-cord
#8
Takeshi Kaneyama, Ryuichi Shirasaki
The dI1 commissural axons in the developing spinal cord, upon crossing the midline through the floor plate, make a sharp turn to grow rostrally. These post-crossing axons initially just extend adjacent to the floor plate without entering nearby motor columns. However, it remains poorly characterized how these post-crossing dI1 axons behave subsequently to this process. In the present study, to address this issue, we examined in detail the behavior of post-crossing dI1 axons in mice, using the Atoh1 enhancer-based conditional expression system that enables selective and sparse labeling of individual dI1 axons, together with Hb9 and ChAT immunohistochemistry for precise identification of spinal motor neurons (MNs)...
May 11, 2018: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29740017/atoh1-rfx1-rfx3-transcription-factors-facilitate-the-differentiation-and-characterisation-of-inner-ear-hair-cell-like-cells-from-patient-specific-induced-pluripotent-stem-cells-harbouring-a8344g-mutation-of-mitochondrial-dna
#9
Yen-Chun Chen, Chia-Ling Tsai, Yau-Huei Wei, Yu-Ting Wu, Wei-Ting Hsu, Hung-Ching Lin, Yi-Chao Hsu
Degeneration or loss of inner ear hair cells (HCs) is irreversible and results in sensorineural hearing loss (SHL). Human-induced pluripotent stem cells (hiPSCs) have been employed in disease modelling and cell therapy. Here, we propose a transcription factor (TF)-driven approach using ATOH1 and regulatory factor of x-box (RFX) genes to generate HC-like cells from hiPSCs. Our results suggest that ATOH1/RFX1/RFX3 could significantly increase the differentiation capacity of iPSCs into MYO7AmCherry -positive cells, upregulate the mRNA expression levels of HC-related genes and promote the differentiation of HCs with more mature stereociliary bundles...
April 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29718413/understanding-molecular-evolution-and-development-of-the-organ-of-corti-can-provide-clues-for-hearing-restoration
#10
Israt Jahan, Karen L Elliott, Bernd Fritzsch
The mammalian hearing organ is a stereotyped cellular assembly with orderly innervation: two types of spiral ganglion neurons (SGNs) innervate two types of differentially distributed hair cells (HCs). HCs and SGNs evolved from single neurosensory cells through gene multiplication and diversification. Independent regulation of HCs and neuronal differentiation through expression of basic Helix-loop-Helix transcription factors (bHLH TFs: Atoh1, Neurog1, Neurod1) led to the evolution of vestibular HC assembly and their unique type of innervation...
April 26, 2018: Integrative and Comparative Biology
https://www.readbyqxmd.com/read/29553487/sox2-haploinsufficiency-primes-regeneration-and-wnt-responsiveness-in-the-mouse-cochlea
#11
Patrick J Atkinson, Yaodong Dong, Shuping Gu, Wenwen Liu, Elvis Huarcaya Najarro, Tomokatsu Udagawa, Alan G Cheng
During development, Sox2 is indispensable for cell division and differentiation, yet its roles in regenerating tissues are less clear. Here, we used combinations of transgenic mouse models to reveal that Sox2 haploinsufficiency (Sox2haplo) increases rather than impairs cochlear regeneration in vivo. Sox2haplo cochleae had delayed terminal mitosis and ectopic sensory cells, yet normal auditory function. Sox2haplo amplified and expanded domains of damage-induced Atoh1+ transitional cell formation in neonatal cochlea...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29548943/multiple-zebrafish-atoh1-genes-specify-a-diversity-of-neuronal-types-in-the-zebrafish-cerebellum
#12
Chelsea U Kidwell, Chen-Ying Su, Masahiko Hibi, Cecilia B Moens
A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum...
June 1, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29397531/a-simplified-method-for-generating-purkinje-cells-from-human-induced-pluripotent-stem-cells
#13
Lauren M Watson, Maggie M K Wong, Jane Vowles, Sally A Cowley, Esther B E Becker
The establishment of a reliable model for the study of Purkinje cells in vitro is of particular importance, given their central role in cerebellar function and pathology. Recent advances in induced pluripotent stem cell (iPSC) technology offer the opportunity to generate multiple neuronal subtypes for study in vitro. However, to date, only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce. Here, we describe a simplified method for the reproducible generation of Purkinje cells from human iPSCs...
February 3, 2018: Cerebellum
https://www.readbyqxmd.com/read/29336137/-in-vitro-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-to-hair-cells-using-growth-factors
#14
Mohammad-Reza Mahmoudian-Sani, Morteza Hashemzadeh-Chaleshtori, Mohammad-Saeid Jami, Massoud Saidijam
OBJECTIVE: In this study, we attempted to differentiated human bone marrow-derived mesenchymal stem cells (hBMSCs) to auditory hair cells using growth factors. METHODS: Retinoic acid (RA), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) were added to hBMSCs cell culture medium. The cells were evaluated morphologically and the expression of SOX2, POU4F3, MYO7A, and Calretinin at mRNA level and ATOH1 mRNA and protein expression. RESULTS: After treatment with the growth factors, the morphology of the cells did not change, but evaluation of gene expression at the mRNA level increased the expression of the ATOH1, SOX2, and POU4F3 markers...
December 1, 2017: International Tinnitus Journal
https://www.readbyqxmd.com/read/29323051/notch-pathway-inhibitor-dapt-enhances-atoh1-activity-to-generate-new-hair-cells-in-situ-in-rat-cochleae
#15
Wen-Wei Luo, Zhao Han, Dong-Dong Ren, Xin-Wei Wang, Fang-Lu Chi, Juan-Mei Yang
Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321651/auditory-neural-activity-in-congenitally-deaf-mice-induced-by-infrared-neural-stimulation
#16
Xiaodong Tan, Israt Jahan, Yingyue Xu, Stuart Stock, Changyow Claire Kwan, Carmen Soriano, Xianghui Xiao, Jaime García-Añoveros, Bernd Fritzsch, Claus-Peter Richter
To determine whether responses during infrared neural stimulation (INS) result from the direct interaction with spiral ganglion neurons (SGNs), we tested three genetically modified deaf mouse models: Atoh1-cre; Atoh1 f/f (Atoh1 conditional knockout, CKO), Atoh1-cre; Atoh1 f/kiNeurog1 (Neurog1 knockin, KI), and the Vglut3 knockout (Vglut3 -/- ) mice. All animals were exposed to tone bursts and clicks up to 107 dB (re 20 µPa) and to INS, delivered with a 200 µm optical fiber. The wavelength (λ) was 1860 nm, the radiant energy (Q) 0-800 µJ/pulse, and the pulse width (PW) 100-500 µs...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317485/meis1-coordinates-cerebellar-granule-cell-development-by-regulating-pax6-transcription-bmp-signaling-and-atoh1-degradation
#17
Tomoo Owa, Shinichiro Taya, Satoshi Miyashita, Mariko Yamashita, Toma Adachi, Koyo Yamada, Miwa Yokoyama, Shogo Aida, Tomoki Nishioka, Yukiko U Inoue, Ryo Goitsuka, Takuro Nakamura, Takayoshi Inoue, Kozo Kaibuchi, Mikio Hoshino
Cerebellar granule cell precursors (GCPs) and granule cells (GCs) represent good models to study neuronal development. Here, we report that the transcription factor myeloid ectopic viral integration site 1 homolog (Meis1) plays pivotal roles in the regulation of mouse GC development. We found that Meis1 is expressed in GC lineage cells and astrocytes in the cerebellum during development. Targeted disruption of the Meis1 gene specifically in the GC lineage resulted in smaller cerebella with disorganized lobules...
January 31, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29241683/notch-pathway-signaling-in-the-skin-antagonizes-merkel-cell-development
#18
Gregory J Logan, Margaret C Wright, Adam C Kubicki, Stephen M Maricich
Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin...
February 15, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29233556/contribution-of-atoh1-cells-to-the-homeostasis-repair-and-tumorigenesis-of-the-colonic-epithelium
#19
Fumiaki Ishibashi, Hiromichi Shimizu, Toru Nakata, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Sho Anzai, Reiko Kuno, Sayaka Nagata, Go Ito, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe, Ryuichi Okamoto
ATOH1 is a master transcription factor for the secretory lineage differentiation of intestinal epithelial cells (IECs). However, the comprehensive contribution of ATOH1+ secretory lineage IECs to the homeostasis, repair, and tumorigenesis of the intestinal epithelium remains uncertain. Through our ATOH1+ cell-lineage tracing, we show here that a definite number of ATOH1+ IECs retain stem cell properties and can form ATOH1+ IEC-derived clonal ribbons (ATOH1+ ICRs) under completely homeostatic conditions. Interestingly, colonic ATOH1+ IECs appeared to exhibit their stem cell function more frequently compared with those of the small intestine...
January 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29168692/jak2-mediated-phosphorylation-of-atoh1-is-critical-for-medulloblastoma-growth
#20
Tiemo J Klisch, Anna Vainshtein, Akash J Patel, Huda Y Zoghbi
Treatment for medulloblastoma, the most common malignant brain tumor in children, remains limited to surgical resection, radiation, and traditional chemotherapy; with long-term survival as low as 50-60% for Sonic Hedgehog (Shh)-type medulloblastoma. We have shown that the transcription factor Atonal homologue 1 (Atoh1) is required for Shh-type medulloblastoma development in mice. To determine whether reducing either Atoh1 levels or activity in tumors after their development is beneficial, we studied Atoh1 dosage and modifications in Shh-type medulloblastoma...
November 23, 2017: ELife
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