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Espina, J. A.

Publications and source records attributed to Espina, J. A..

2 recordsLinked to original sources

Nuclear deformability facilitates apical nuclear migration in the developing zebrafish retina

Nuclear positioning is an important aspect of cell and developmental biology. One example is the apical positioning of nuclei in retinal and other neuroepithelia. Here, apical nuclear migration is crucial for correct tissue formation. Cytoskeletal mechanisms that drive nuclei to the apical side have been explored. Yet, whether also nuclear properties influence apical nuclear migration remained comparatively less understood. Lamin A/C expression levels have been shown to be directly related to nuclear deformability. Further, it was shown that many nuclei in early development, including neuroepithelial nuclei, express only low levels of Lamin A/C. Thus, we asked whether increased expression of Lamin A in the densely packed zebrafish retinal neuroepithelium affects nuclear migration phenomena. We find that overexpressing Lamin A in retinal nuclei of single cells or in the whole tissue increased nuclear stiffness and consequently impaired apical positioning. Interestingly, also nuclei of control cells embedded in a Lamin A overexpressing environment displayed impaired apical nuclear migration. When Lamin A is overexpressed at the tissue level this further leads to a delay in mitotic entry. Thus, nuclear material properties, within cells but also in the surrounding environment, can influence nuclear and cell behavior in densely packed neuroepithelia. Overall, this work quantitatively shows a relevance of low Lamin A/C levels in early neuroepithelial development. These findings are most likely also applicable for other developing tissues which feature nuclear and cell motion through crowded environments.

developmental biology↗

Microtubule deacetylation reduces cell stiffness to allow the onset of collective cell migration in vivo

Embryogenesis, tissue repair and cancer metastasis rely on collective cell migration (CCM). In vitro studies propose that migrating cells are stiffer when exposed to stiff substrates, known to allow CCM, but softer when plated in compliant non-permissive surfaces. Here, by combining in vivo atomic force microscopy (iAFM) and modelling we reveal that to collectively migrate in vivo, cells require to dynamically decrease their stiffness in response to the temporal stiffening of their native substrate. Moreover, molecular and mechanical perturbations of embryonic tissues uncover that this unexpected cell mechanical response is achieved by a new mechanosensitive pathway involving Piezo1-mediated microtubule deacetylation. Finally, lowering microtubule acetylation and consequently cell stiffness was sufficient to allow CCM in soft non-permissive substrates, suggesting that a fixed value of substrate stiffness is not as essential for CCM as it is reaching an optimal cell-to-substrate stiffness value. These in vivo insights on cell-to-substrate mechanical interplay have major implications to our re-interpretation of physiological and pathological contexts.

cell biology↗