E-cadherin and the Differentiation of Mammalian Vestibular Hair Cells

Hackett, Lucy; Davies, D. R.; Helyer, Richard J; Kennedy, Helen J; Kros, Corné J.; Lawlor, Patrick; Rivolta, Marcelo N.; Holley, Matthew C.

doi:10.1006/excr.2002.5574

Cited by 26 publications

(24 citation statements)

References 67 publications

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“…It is conceivable that cell-cell interactions necessary for the propagation of polarity signals are different in hearing and balance organs owing to their distinct mosaic patterns of hair cells and support cells. Moreover, distinct expression patterns of cell-adhesion molecules may contribute to differences in cell-adhesion and cytoskeletal organization between hearing and balance organs (Hackett et al, 2002;Simonneau et al, 2003). Interestingly, there is evidence that an additional, as yet unidentified, patterning event operates together with the tissue polarity pathway to regulate PCP in the utricular macula (Deans et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms

Sipe

2011

Development

114

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SUMMARYAuditory hair cells represent one of the most prominent examples of epithelial planar polarity. In the auditory sensory epithelium, planar polarity of individual hair cells is defined by their V-shaped hair bundle, the mechanotransduction organelle located on the apical surface. At the tissue level, all hair cells display uniform planar polarity across the epithelium. Although it is known that tissue planar polarity is controlled by non-canonical Wnt/planar cell polarity (PCP) signaling, the hair cell-intrinsic polarity machinery that establishes the V-shape of the hair bundle is poorly understood. Here, we show that the microtubule motor subunit Kif3a regulates hair cell polarization through both ciliary and non-ciliary mechanisms. Disruption of Kif3a in the inner ear led to absence of the kinocilium, a shortened cochlear duct and flattened hair bundle morphology. Moreover, basal bodies are mispositioned along both the apicobasal and planar polarity axes of mutant hair cells, and hair bundle orientation was uncoupled from the basal body position. We show that a non-ciliary function of Kif3a regulates localized cortical activity of p21-activated kinases (PAK), which in turn controls basal body positioning in hair cells. Our results demonstrate that Kif3a-PAK signaling coordinates planar polarization of the hair bundle and the basal body in hair cells, and establish Kif3a as a key component of the hair cell-intrinsic polarity machinery, which acts in concert with the tissue polarity pathway.

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Section: Discussionmentioning

confidence: 99%

Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms

Sipe

2011

Development

114

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“…These included the previously described epithelial cell-specific marker Epithelium-specific ets-1 (ESE-1) (Oettgen et al 1999;Redmond et al 2011), the hair cell specific markers Atoh1 and Myosin VI, the supporting cell associated cyclin-dependent kinase inhibitor p27 kip1 , the proliferation control marker FGFR1 and the vestibular cell differentiation marker E-cadherin (CDH1) (Hackett et al 2002). IF staining revealed positive protein expression of all specified markers over 100% of the observed cell population.…”

Section: Resultsmentioning

confidence: 96%

“…Previous studies using murine vestibular sensory epithelia have shown E-cadherin to be downregulated in differentiating hair cells, but are maintained in the surrounding supporting cells. In addition, this downregulation in differentiating hair cells only occurs after they have passed through terminal mitosis and continues until differentiation is complete (Hackett et al 2002). During cochlear development, p27 kip1 expression is the process responsible for enforcing the temporal separation between cell cycle exit (terminal mitosis) and cell differentiation , with a similar sequence of events postulated to take place in the vestibular system (Chen and Segil 1999).…”

Section: Resultsmentioning

confidence: 97%

In vitro cultured primary cells from a human utricle explant possesses hair cell like characteristics

Marano

Redmond

2011

J Mol Hist

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The utricle is the enlarged portion of the membranous labyrinth of the inner ear and is essential for balance. It comprises of fine hair cells (mechanoreceptors), supporting cells and calcareous otoliths. Utricle cells are considered to be post-mitotic and possess a limited capacity for regeneration. Unlike birds and reptiles, mammalian mechanosensory hair cells do not regenerate. The in vitro culture of primary cells from the utricle and other inner ear structures of mammals have proven difficult. Presented here for the first time is the culture of primary cells derived from an explant of an adult human utricle, without any intervention or manipulation. Cells were proliferative until cellular quiescence occurred during passage six. Cell morphology was atypical of epithelial cells, appearing as a homogenous, slightly elongated population. Analysis of cultured utricle cells by immunofluorescent staining (IF) and reverse transcriptase polymerase chain reaction (RT-PCR) have shown these cells to possess epithelial (Epithelium-specific ets-1 (ESE-1)), supporting hair cell (p27(Kip1)), and hair cell specific (Atoh1 and Myosin VI) markers. Additionally, RT-PCR revealed positive gene expression for the proliferation control marker fibroblast growth factor receptor 1 (FGFR1) and negative gene expression for E-cadherin (CDH1), a vestibular cell differentiation marker.

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“…␤ -Catenin is known to play an important role in both cell-cell adhesion and signal transduction associated with cell proliferation. E-cadherin has been reported to be expressed in supporting cells and downregulated in differentiating hair cells, and that constitutive expression in a conditionally immortal utricular macula cell line inhibits the progression of hair cell differentiation [Hackett et al, 2002]. Protocadherin ␣ 13 (Pcdha13) is an associated gene that was identifi ed in our library.…”

Section: Discussionmentioning

confidence: 99%

In silico Analysis of 2085 Clones from a Normalized Rat Vestibular Periphery 3′ cDNA Library

Roche

Wackym²,

Cioffi³

et al. 2005

Audiol Neurotol

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The inserts from 2400 cDNA clones isolated from a normalized Rattus norvegicus vestibular periphery cDNA library were sequenced and characterized. The Wackym-Soares vestibular 3′ cDNA library was constructed from the saccular and utricular maculae, the ampullae of all three semicircular canals and Scarpa’s ganglia containing the somata of the primary afferent neurons, microdissected from 104 male and female rats. The inserts from 2400 randomly selected clones were sequenced from the 5′ end. Each sequence was analyzed using the BLAST algorithm compared to the Genbank nonredundant, rat genome, mouse genome and human genome databases to search for high homology alignments. Of the initial 2400 clones, 315 (13%) were found to be of poor quality and did not yield useful information, and therefore were eliminated from the analysis. Of the remaining 2085 sequences, 918 (44%) were found to represent 758 unique genes having useful annotations that were identified in databases within the public domain or in the published literature; these sequences were designated as known characterized sequences. 1141 sequences (55%) aligned with 1011 unique sequences had no useful annotations and were designated as known but uncharacterized sequences. Of the remaining 26 sequences (1%), 24 aligned with rat genomic sequences, but none matched previously described rat expressed sequence tags or mRNAs. No significant alignment to the rat or human genomic sequences could be found for the remaining 2 sequences. Of the 2085 sequences analyzed, 86% were singletons. The known, characterized sequences were analyzed with the FatiGO online data-mining tool (http://fatigo.bioinfo.cnio.es/) to identify level 5 biological process gene ontology (GO) terms for each alignment and to group alignments with similar or identical GO terms. Numerous genes were identified that have not been previously shown to be expressed in the vestibular system. Further characterization of the novel cDNA sequences may lead to the identification of genes with vestibular-specific functions. Continued analysis of the rat vestibular periphery transcriptome should provide new insights into vestibular function and generate new hypotheses. Physiological studies are necessary to further elucidate the roles of the identified genes and novel sequences in vestibular function.

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E-cadherin and the Differentiation of Mammalian Vestibular Hair Cells

Cited by 26 publications

References 67 publications

Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms

Kif3a regulates planar polarization of auditory hair cells through both ciliary and non-ciliary mechanisms

In vitro cultured primary cells from a human utricle explant possesses hair cell like characteristics

In silico Analysis of 2085 Clones from a Normalized Rat Vestibular Periphery 3′ cDNA Library

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