384 research outputs found

    Zona Pellucida Domain-Containing Protein β-Tectorin is Crucial for Zebrafish Proper Inner Ear Development

    Get PDF
    BACKGROUND: The zona pellucida (ZP) domain is part of many extracellular proteins with diverse functions from structural components to receptors. The mammalian β-tectorin is a protein of 336 amino acid residues containing a single ZP domain and a putative signal peptide at the N-terminus of the protein. It is 1 component of a gel-like structure called the tectorial membrane which is involved in transforming sound waves into neuronal signals and is important for normal auditory function. β-Tectorin is specifically expressed in the mammalian and avian inner ear. METHODOLOGY/PRINCIPAL FINDINGS: We identified and cloned the gene encoding zebrafish β-tectorin. Through whole-mount in situ hybridization, we demonstrated that β-tectorin messenger RNA was expressed in the otic placode and specialized sensory patch of the inner ear during zebrafish embryonic stages. Morpholino knockdown of zebrafish β-tectorin affected the position and number of otoliths in the ears of morphants. Finally, swimming behaviors of β-tectorin morphants were abnormal since the development of the inner ear was compromised. CONCLUSIONS/SIGNIFICANCE: Our results reveal that zebrafish β-tectorin is specifically expressed in the zebrafish inner ear, and is important for regulating the development of the zebrafish inner ear. Lack of zebrafish β-tectorin caused severe defects in inner ear formation of otoliths and function

    Mammalian Otolin: A Multimeric Glycoprotein Specific to the Inner Ear that Interacts with Otoconial Matrix Protein Otoconin-90 and Cerebellin-1

    Get PDF
    The mammalian otoconial membrane is a dense extracellular matrix containing bio-mineralized otoconia. This structure provides the mechanical stimulus necessary for hair cells of the vestibular maculae to respond to linear accelerations and gravity. In teleosts, Otolin is required for the proper anchoring of otolith crystals to the sensory maculae. Otoconia detachment and subsequent entrapment in the semicircular canals can result in benign paroxysmal positional vertigo (BPPV), a common form of vertigo for which the molecular basis is unknown. Several cDNAs encoding protein components of the mammalian otoconia and otoconial membrane have recently been identified, and mutations in these genes result in abnormal otoconia formation and balance deficits.Here we describe the cloning and characterization of mammalian Otolin, a protein constituent of otoconia and the otoconial membrane. Otolin is a secreted glycoprotein of ∼70 kDa, with a C-terminal globular domain that is homologous to the immune complement C1q, and contains extensive posttranslational modifications including hydroxylated prolines and glycosylated lysines. Like all C1q/TNF family members, Otolin multimerizes into higher order oligomeric complexes. The expression of otolin mRNA is restricted to the inner ear, and immunohistochemical analysis identified Otolin protein in support cells of the vestibular maculae and semi-circular canal cristae. Additionally, Otolin forms protein complexes with Cerebellin-1 and Otoconin-90, two protein constituents of the otoconia, when expressed in vitro. Otolin was also found in subsets of support cells and non-sensory cells of the cochlea, suggesting that Otolin is also a component of the tectorial membrane.Given the importance of Otolin in lower organisms, the molecular cloning and biochemical characterization of the mammalian Otolin protein may lead to a better understanding of otoconial development and vestibular dysfunction

    Cell Type–Specific Transcriptome Analysis Reveals a Major Role for Zeb1 and miR-200b in Mouse Inner Ear Morphogenesis

    Get PDF
    Cellular heterogeneity hinders the extraction of functionally significant results and inference of regulatory networks from wide-scale expression profiles of complex mammalian organs. The mammalian inner ear consists of the auditory and vestibular systems that are each composed of hair cells, supporting cells, neurons, mesenchymal cells, other epithelial cells, and blood vessels. We developed a novel protocol to sort auditory and vestibular tissues of newborn mouse inner ears into their major cellular components. Transcriptome profiling of the sorted cells identified cell type–specific expression clusters. Computational analysis detected transcription factors and microRNAs that play key roles in determining cell identity in the inner ear. Specifically, our analysis revealed the role of the Zeb1/miR-200b pathway in establishing epithelial and mesenchymal identity in the inner ear. Furthermore, we detected a misregulation of the ZEB1 pathway in the inner ear of Twirler mice, which manifest, among other phenotypes, malformations of the auditory and vestibular labyrinth. The association of misregulation of the ZEB1/miR-200b pathway with auditory and vestibular defects in the Twirler mutant mice uncovers a novel mechanism underlying deafness and balance disorders. Our approach can be employed to decipher additional complex regulatory networks underlying other hearing and balance mouse mutants

    Search for Neutral Heavy Leptons Produced in Z Decays

    Get PDF
    Weak isosinglet Neutral Heavy Leptons (νm\nu_m) have been searched for using data collected by the DELPHI detector corresponding to 3.3×1063.3\times 10^{6} hadronic~Z0^{0} decays at LEP1. Four separate searches have been performed, for short-lived νm\nu_m production giving monojet or acollinear jet topologies, and for long-lived νm\nu_m giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio BR(BR(Z0νmν)^0\rightarrow \nu_m \overline{\nu}) of about 1.3×1061.3\times10^{-6} at 95\% confidence level for νm\nu_m masses between 3.5 and 50 GeV/c2c^2. Outside this range the limit weakens rapidly with the νm\nu_m mass. %Special emphasis has been given to the search for monojet--like topologies. One event %has passed the selection, in agreement with the expectation from the reaction: %e+eˉννˉe^+e^- \rightarrow\ell \bar\ell \nu\bar\nu. The results are also interpreted in terms of limits for the single production of excited neutrinos

    Search for new phenomena using single photon events in the DELPHI detector at LEP

    Get PDF
    Data are presented on the reaction \epem~\into~\gamma + no other detected particle at center-of-mass energies, \sqs = 89.48 GeV, 91.26 GeV and 93.08 GeV. The cross section for this reaction is related directly to the number of light neutrino generations which couple to the \zz boson, and to several other phenomena such as excited neutrinos, the production of an invisible `X' particle, a possible magnetic moment of the tau neutrino, and neutral monojets. Based on the observed number of single photon events, the number of light neutrinos which couple to the \zz is measured to be N_\nu = 3.15 \pm 0.34. No evidence is found for anomalous production of energetic single photons, and upper limits at the 95\% confidence level are determined for excited neutrino production (BR < 4-9 \times 10^{-6}), production of an invisible `X' particle (\sigma < 0.1 pb), and the magnetic moment of the tau neutrino (< 5.2 \times 10^{-6} \mu_B). No event with the topology of a neutral monojet is found, and this corresponds to the limit \sigma < 0.044/\epsilon pb at the 95\% confidence level, where \epsilon is the unknown overall monojet detection efficiency

    Measurement of inclusive π0\pi^{0} production in hadronic Z0Z^{0} decays

    Get PDF
    An analysis is presented of inclusive \pi^0 production in Z^0 decays measured with the DELPHI detector. At low energies, \pi^0 decays are reconstructed by \linebreak using pairs of converted photons and combinations of converted photons and photons reconstructed in the barrel electromagnetic calorimeter (HPC). At high energies (up to x_p = 2 \cdot p_{\pi}/\sqrt{s} = 0.75) the excellent granularity of the HPC is exploited to search for two-photon substructures in single showers. The inclusive differential cross section is measured as a function of energy for {q\overline q} and {b \bar b} events. The number of \pi^0's per hadronic Z^0 event is N(\pi^0)/ Z_{had}^0 = 9.2 \pm 0.2 \mbox{(stat)} \pm 1.0 \mbox{(syst)} and for {b \bar b}~events the number of \pi^0's is {\mathrm N(\pi^0)/ b \overline b} = 10.1 \pm 0.4 \mbox{(stat)} \pm 1.1 \mbox{(syst)} . The ratio of the number of \pi^0's in b \overline b events to hadronic Z^0 events is less affected by the systematic errors and is found to be 1.09 \pm 0.05 \pm 0.01. The measured \pi^0 cross sections are compared with the predictions of different parton shower models. For hadronic events, the peak position in the \mathrm \xi_p = \ln(1/x_p) distribution is \xi_p^{\star} = 3.90^{+0.24}_{-0.14}. The average number of \pi^0's from the decay of primary \mathrm B hadrons is found to be {\mathrm N} (B \rightarrow \pi^0 \, X)/\mbox{B hadron} = 2.78 \pm 0.15 \mbox{(stat)} \pm 0.60 \mbox{(syst)}
    corecore