Biology subjects

Gianoli, F.

Publications and source records attributed to Gianoli, F..

4 recordsLinked to original sources

bioRxiv2026

Vangl2 acts in distinct cell types to establish bidirectional hair-bundle polarity and maintains tissue-wide alignment in zebrafish neuromasts

The conserved core planar cell polarity (PCP) pathway orients cells and subcellular structures within an epithelium through asymmetric protein localization and intercellular communication. In vestibular organs and lateral-line neuromasts, mechanosensory hair cells are interspersed among support cells and form opposing hair-bundle orientations along a shared axis, enabling bidirectional sensitivity to head motion and water flow, respectively. In zebrafish neuromasts, Notch-mediated lateral inhibition gives rise to two hair-cell populations, distinguished by differential Emx2 expression, that orient their cell-intrinsic polarity machinery differently relative to a PCP-dependent tissue-wide axis. However, it remains unclear how PCP proteins are organized across hair cells and support cells to achieve both opposing hair-bundle orientations and tissue-wide alignment, and whether PCP signaling remains required after hair-bundle polarity is established. Combining quantitative spatial mapping of the core PCP protein Vangl2 with cell-type-specific and temporally controlled protein degradation, we show that hair cells and support cells make distinct yet coordinated contributions to the polarized Vangl2 organization within neuromasts and to bidirectional hair-bundle polarity. Support-cell Vangl2 facilitates tissue-wide alignment of hair bundles along the anteroposterior axis, whereas hair-cell Vangl2 is required to generate opposing hair-bundle orientations along this axis. Vangl2 degradation after hair bundles have formed disrupts their tissue-wide alignment, showing that planar polarity is actively maintained rather than fixed after establishment. Together, these findings reveal how Vangl2-dependent PCP signaling is distributed across distinct cell types within a heterogeneous epithelium to generate opposing polarity outcomes and remains necessary to preserve tissue-level planar organization.

developmental biology↗

bioRxiv2021

Fast adaptation of cooperative channels engendersHopf bifurcations in auditory hair cells

Since the pioneering work of Thomas Gold published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Termed the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ears mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive--especially at the high frequencies characteristic of mammalian hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has previously been proposed that a cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here, we ground our study on our previous model of hair-cell mechanotransduction, which relied on the cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, our model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. In contrast to the myosin-based mechanism, responsible for low-frequency relaxation oscillations in the vestibular hair cells of amphibians, the current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the single mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of mammalian hearing. SIGNIFICANCEHow the inner ear amplifies incident sounds at audible frequencies of several kilohertz is a key question that has remained unanswered despite decades of research into several candidate mechanisms. Here, we model the behavior of hair cells, the sensory receptors of the inner ear, and show that they can undergo oscillatory instabilities called Hopf bifurcations due to the effect of Ca2+ on the cooperative opening and closing of mechanotransduction ion channels. Close to the bifurcation point, a hair cell behaves as a nonlinear oscillator that can amplify its input on a cycle-by-cycle basis. We find that our proposed mechanism can operate in the kilohertz range.

biophysics↗

bioRxiv2021

Rapid mechanical stimulation of inner-ear hair cells by photonic pressure

Hair cells, the receptors of the inner ear, detect sounds by transducing mechanical vibrations into electrical signals. From the top surface of each hair cell protrudes a mechanical antenna, the hair bundle, which the cell uses to detect and amplify auditory stimuli, thus sharpening frequency selectivity and providing a broad dynamic range. Current methods for mechanically stimulating hair bundles are too slow to encompass the frequency range of mammalian hearing and are plagued by inconsistencies. To overcome these challenges, we have developed a method to move individual hair bundles with photonic force. This technique uses an optical fiber whose tip is tapered to a diameter of a few micrometers and endowed with a ball lens to minimize divergence of the light beam. Here we describe the fabrication, characterization, and application of this optical system and demonstrate the rapid application of photonic force to vestibular and cochlear hair cells.

neuroscience↗

bioRxiv2019

The development of cooperative channels explains the maturation of hair cell’s mechanotransduction

Hearing relies on the conversion of mechanical stimuli into electrical signals. In vertebrates, this process of mechano-electrical transduction (MET) is performed by specialized receptors of the inner ear, the hair cells. Each hair cell is crowned by a hair bundle, a cluster of microvilli that pivot in response to sound vibrations, causing the opening and closing of mechanosensitive ion channels. Mechanical forces are projected onto the channels by molecular springs called tip links. Each tip link is thought to connect to a small number of MET channels that gate cooperatively and operate as a single transduction unit. Pushing the hair bundle in the excitatory direction opens the channels, after which they rapidly reclose in a process called fast adaptation. It has been experimentally observed that the hair cells biophysical properties mature gradually during postnatal development: the maximal transduction current increases, sensitivity sharpens, transduction occurs at smaller hair-bundle displacements, and adaptation becomes faster. Similar observations have been reported during tip-link regeneration after acoustic damage. Moreover, when measured at intermediate developmental stages, the kinetics of fast adaptation varies in a given cell depending on the magnitude of the imposed displacement. The mechanisms underlying these seemingly disparate observations have so far remained elusive. Here, we show that these phenomena can all be explained by the progressive addition of MET channels of constant properties, which populate the hair bundle first as isolated entities, then progressively as clusters of more sensitive, cooperative MET channels. As the proposed mechanism relies on the difference in biophysical properties between isolated and clustered channels, this work highlights the importance of cooperative interactions between mechanosensitive ion channels for hearing.\n\nSIGNIFICANCEHair cells are the sensory receptors of the inner ear that convert mechanical stimuli into electrical signals transmitted to the brain. Sensitivity to mechanical stimuli and the kinetics of mechanotransduction currents change during hair-cell development. The same trend, albeit on a shorter timescale, is also observed during hair-cell recovery from acoustic trauma. Furthermore, the current kinetics in a given hair cell depends on the stimulus magnitude, and the degree of that dependence varies with development. These phenomena have so far remained unexplained. Here, we show that they can all be reproduced using a single unifying mechanism: the progressive formation of channel pairs, in which individual channels interact through the lipid bilayer and gate cooperatively.

biophysics↗