Wnt signaling during cochlear development

Munnamalai, Vidhya; Fekete, Donna M.

doi:10.1016/j.semcdb.2013.03.008

Cited by 64 publications

(70 citation statements)

References 90 publications

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“…The Fgf pathway initiates dld and subsequently Notch signaling in the mouse cochlea, chicken inner ear, and zebrafish lateral line neuromasts (23,60). Both pathways are active in 5-dpf untreated neuromasts (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The Wnt/ β-catenin, Notch, Jak/Stat, Bmp, and Fgf pathways are important for hair cell development as well as for the regeneration of hair cells in fish and chick epithelia (15,23,43). Our understanding of which pathways act upstream and how these pathways affect each other is still very limited.…”

Section: Resultsmentioning

confidence: 99%

“…Likewise, a previous expression study of the regenerating zebrafish ear was performed 24 h after the larvae were exposed to noise that does not cause death simultaneously in all hair cells (36). Further adding to the complexity, genes are used repeatedly during hair cell development and can turn from an activator into a repressor (23). We have selected the zebrafish lateral line tissue to elucidate the gene-expression patterns triggered by hair cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Our analyses focused on pathways involved in hair cell development as they might be reused during regeneration (15,23,43,78,79). For example, Wnt/β-catenin signaling is crucial for the development of many organs across the animal kingdom (80).…”

Section: Discussionmentioning

confidence: 99%

“…Given that mammalian support cells do not respond to hair cell death by proliferating, molecular studies in chick have focused on identifying the mitogenic signals as well as the target genes that induce re-entering of the cell cycle in support cells (11,(20)(21)(22). For example, the transcription factors Atoh1 and Sox2 and the Wnt/β-catenin and Notch pathways have been shown to play crucial roles (23), and gene-expression analyses using microarrays have identified hundreds of genes involved in chick hair cell regeneration (18,24).…”

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confidence: 99%

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Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

Jiang

Romero‐Carvajal

Haug

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

136

152

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Deafness caused by the terminal loss of inner ear hair cells is one of the most common sensory diseases. However, nonmammalian animals (e.g., birds, amphibians, and fish) regenerate damaged hair cells. To understand better the reasons underpinning such disparities in regeneration among vertebrates, we set out to define at high resolution the changes in gene expression associated with the regeneration of hair cells in the zebrafish lateral line. We performed RNA-Seq analyses on regenerating support cells purified by FACS. The resulting expression data were subjected to pathway enrichment analyses, and the differentially expressed genes were validated in vivo via whole-mount in situ hybridizations. We discovered that cell cycle regulators are expressed hours before the activation of Wnt/β-catenin signaling following hair cell death. We propose that Wnt/β-catenin signaling is not involved in regulating the onset of proliferation but governs proliferation at later stages of regeneration. In addition, and in marked contrast to mammals, our data clearly indicate that the Notch pathway is significantly down-regulated shortly after injury, thus uncovering a key difference between the zebrafish and mammalian responses to hair cell injury. Taken together, our findings lay the foundation for identifying differences in signaling pathway regulation that could be exploited as potential therapeutic targets to promote either sensory epithelium or hair cell regeneration in mammals.signaling pathway analysis | RNA sequencing | neuromast | Jak/Stat3 | cdkn1b

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

Jiang

Romero‐Carvajal

Haug

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

136

152

View full text Add to dashboard Cite

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Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

et al. 2017

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Degeneration of the central auditory system, which is characterized by reduced understanding of speech and source localization of sounds, is an important cause of age‐related hearing loss (presbycusis). Accumulating evidence has demonstrated that Wnt/β‐catenin signaling plays an essential role in the development of the auditory system but its potential role in presbycusis remains unclear. In this study, we used a rat model of aging, created by chronic systemic exposure to d ‐galactose ( d ‐gal), and explored changes in Wnt/β‐catenin signaling in the auditory cortex. A decrease in Wnt/β‐catenin signaling in the auditory cortex was found in both naturally aging and d ‐gal‐mimetic aging rats, as indicated by increased GSK 3β activity and decreased β‐catenin activity. Moreover, lithium chloride (Licl), an activator of Wnt signaling pathway, was administered long term to 15‐month‐old d ‐gal‐treated rats. Activation of Wnt/β‐catenin signaling by Licl attenuated d ‐gal‐induced auditory cortex apoptosis and neurodegeneration. Bmi1, a transcription factor implicated in antiaging and resistance to apoptosis, can be modulated by β‐catenin activity. Here, we showed that the expression of Bmi1 was reduced and the expression of its downstream genes, p16 INK 4a , p19 Arf , and p53 were increased in the auditory cortex both of naturally aging and d ‐gal‐mimetic aging rats. In addition, Licl significantly increased Bmi1 expression and reduced p16 INK 4a , p19 Arf , and p53 expression. Our results indicated that decreased Wnt/β‐catenin signaling might participate in the pathogenesis of central presbycusis through modulating the expression of Bmi1. Wnt/β‐catenin signaling might be used as a potential therapeutic target against presbycusis.

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TGF β‐1 and WNT Signaling Pathways Collaboration Associated with Cochlear Implantation Trauma‐Induced Fibrosis

Bas

Anwar

Water

2019

The Anatomical Record

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The crosstalk between TGF‐β1 and WNT pathways has been proven to regulate aspects of the development and tissue homeostasis processes. Recently, it has been demonstrated this collaboration also takes place during fibrotic diseases, where TGF‐β1 activates the WNT/β‐catenin pathway that results in dedifferentiation of fibroblasts into myofibroblasts, increased production of extracellular matrix components and fibrosis. Independent studies show the functions of these molecules during the development of the inner ears in several different species. However, little is known about the collaboration between TGF‐β1 and WNT in the injured inner ear and particularly how this collaboration affects the fibrotic process that often occurs following cochlear implantation. First, we used a cochlear explant model to study the effect of electrode insertion trauma and TGF‐β1 signaling in activation of the WNT pathway. Finally, adult TopGal mutant mice were used in vivo to track the activation of the WNT/β‐catenin in response to EIT. A chronic inflammatory response, increased cell proliferation and tissue remodeling are hallmarks of fibrotic disease. This study explores and highlights the collaboration between the TGF‐β1 and WNT pathways in the trauma‐initiated fibrotic process within the implanted cochlea. WNT signaling is involved in the development of the inner ear and therefore a potential target in hair cell regeneration therapies. However, in light of our observations from the current study, manipulation of the WNT pathway by gene therapy techniques in the pathological ear seems a very complex process with an increased risk of inducing excessive fibrosis thereby compromising the efficacy of implant function. Anat Rec, 303:608–618, 2020. © 2019 American Association for Anatomy

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Wnt signaling during cochlear development

Cited by 64 publications

References 90 publications

Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

Activation of Wnt/β‐catenin signaling by lithium chloride attenuates d‐galactose‐induced neurodegeneration in the auditory cortex of a rat model of aging

TGF β‐1 and WNT Signaling Pathways Collaboration Associated with Cochlear Implantation Trauma‐Induced Fibrosis

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