Biology subjects

Nommick, A.

Publications and source records attributed to Nommick, A..

4 recordsLinked to original sources

bioRxiv2026

A Cell Size-Dependent Competition Between Geometry and Polarity Governs Nuclear and Spindle positioning in Early Embryos

Nuclei and mitotic spindles are actively positioned at defined locations within cells to regulate cell polarity, division and multicellular morphogenesis1-4. Forces generated by cytoskeleton networks regulate the positioning of these organelles and are commonly influenced by extrinsic cues such as cell geometry or polarity5-12. To date, however, most studies have investigated this problem in one given cell type, hampering our understanding for how mechanical systems that position nuclei and spindles may scale during multicellular development. We tracked the spatiotemporal behaviour of centrosomes, nuclei and spindles in early sea urchin embryos from the 1-cell to the [~]1000 cells blastula stage. We found that they are initially located at cell centers, but that they undergo a progressive decentration towards the embryo apical surface, as cells become smaller during development. This apical shift is mediated by microtubule (MTs) pulling forces which are influenced by both cell shapes and apical polarity domains. Using 3D mathematical models and embryo dissections, we propose that MT centering forces that derive from cell geometry decay in strength during development as a consequence of cell size reduction, allowing apical polarity decentering forces to take over. Our results support a self-organized scenario in which polarity cues progressively outcompete cell geometry, to modulate the overall balance of MT forces and pattern nuclear and spindle positioning throughout early embryo development.

cell biology↗

bioRxiv2023

Cell shape anisotropy enhances cytoplasm viscoelastic resistance to stabilize mitotic spindle position during early embryo development

Cell geometry is a key parameter for the regulation of mitotic spindle positioning during early embryo development and tissue morphogenesis. To date, however, we still lack an understanding for how intracellular forces that position, orient or hold mitotic spindles depend on cell geometry. Here, we used in vivo magnetic tweezers to directly measure the forces that maintain the mitotic spindle in the center of sea urchin cells that adopt different shapes during early embryo development. We found that spindles are held by viscoelastic forces that progressively increase in amplitude as cells become more elongated during early development. By coupling direct cell shape manipulations and in vivo force measurements, we establish how spindle associated forces increase in dose dependence with cell shape anisotropy. Cytoplasm flow analysis and hydrodynamic simulations suggest that this geometry-dependent mechanical enhancement results from a stronger hydrodynamic coupling between the spindle and cell boundaries, which dampens cytoplasm flows and spindle mobility as cells become more elongated. These findings establish how cell shape affects spindle associated forces, and suggest a novel mechanism for shape-sensing and division positioning mediated by intracellular hydrodynamics with functional implications for early embryo morphogenesis.

cell biology↗

bioRxiv2021

Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function

Ciliated epithelia perform a variety of essential functions across animal evolution, ranging from locomotion of marine organisms to mucociliary clearance of airways in mammals. These epithelia are composed of multiciliated cells (MCCs) harbouring myriads of motile cilia, which rest on modified centrioles called basal bodies (BBs), and beat coordinately to generate directed fluid flows. Thus, BB biogenesis and organization is central to MCC function. In basal eukaryotes, the coiled-coil domain proteins Lrrcc1 and Ccdc61 were shown to be required for proper BB construction and function. Here, we used the Xenopus embryonic ciliated epidermis to characterize Lrrcc1 and Ccdc61 in vertebrate MCCs. We found that they both encode BB components, with a prominent association to striated rootlets. Knocking down either gene caused defects in BB docking, spacing, and polarization. Moreover, their depletion impaired the apical cytoskeleton, and altered ciliary beating. Consequently, cilia-powered fluid flow was greatly reduced in morphant tadpoles, which displayed enhanced mortality when exposed to pathogenic bacteria. This work illustrates how integration across organizational scales make elementary BB components essential for the emergence of the physiological function of ciliated epithelia.

developmental biology↗

bioRxiv2019

Active mucus-cilia hydrodynamic coupling drives self-organisation of human bronchial epithelium

The respiratory tract is protected by mucus, a complex fluid transported along the epithelial surface by the coordinated beating of millions of microscopic cilia, hence the name of mucociliary clearance. Its impairment is a strong marker of severe chronic respiratory diseases. Yet, the relationship between ciliary density and the spatial scale of mucus transport, as well as the mechanisms that drive ciliary-beat orientations during ciliogenesis are much debated. Here, we show on polarized human bronchial epithelia that mucus swirls and circular orientational order of the underlying ciliary beats emerge and grow during ciliogenesis, until a macroscopic mucus transport is achieved for physiological ciliary densities. By establishing that the macroscopic ciliary-beat order is lost and recovered by removing and adding mucus respectively, we demonstrate that cilia/mucus hydrodynamic interactions govern the collective dynamics of ciliary-beat directions. We propose a two-dimensional model that predicts a phase diagram of mucus transport in accordance with the experiments. It paves the way to a predictive in-silico modeling of bronchial mucus transport in health and disease.

biophysics↗