Biology subjects

Espina, J. A.

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

4 recordsLinked to original sources

bioRxiv2025

Mechanical control of histone serotonylation initiates neural crest migration in vivo

Collective cell migration (CCM) is pivotal in several biological contexts, and posttranslational modifications of histones are essential to initiate this process1-3. Here, we show that a recently discovered chromatin mark, termed histone serotonylation4, is involved in the collective migration of cranial neural crest cells - an embryonic multipotent stem cell population5. Our in vivo data reveal that histone serotonylation appears in neural crest cells just before they start migrating and that its occurrence is essential to initiate their CCM. Surprisingly, we found that stiffening of the neural crest migratory substrate, the mesoderm, induces histone serotonylation by promoting nuclear translocation of transglutaminase 2 (Tgm2), the enzyme responsible for adding serotonin to histones4. Moreover, mechanical and molecular perturbations demonstrate that mechanical shuttling of Tgm2 into the nucleus, with concomitant increases in histone serotonylation, are both required and sufficient to allow CCM in vivo. Furthermore, integrated chromatin immunoprecipitation and RNA sequencing analyses uncover a transcriptional module, which is enabled by histone serotonylation in response to mesoderm stiffening. Altogether, our results provide in vivo evidence showing that tissue stiffening leads to increased levels of histone serotonylation to reinforce permissive patterns of gene expression, supporting the switch from non-migratory to migratory cell states.

developmental biology↗

bioRxiv2025

Piezo1-Yap1 signalling translates tissue mechanics into regenerative cell states.

Epimorphic regeneration encompasses several stages, such as wound healing, formation of a regenerative bud and regenerative outgrowth. The signatures that define each stage have been well studied, yet little is known about the mechanisms that coordinate cell state transitions across regenerative stages. Here, we show that stiffening of wounded epithelial tissues is essential for the formation of a prospective regenerative bud and, in turn, for the transition from wound healing to bud formation. Mechanistically, to detect prospective bud stiffening, cells use a mechanosensitive cascade involving Piezo1-dependent Yap1 activation. We also determined that this cascade is required for the acquisition of a transcriptional profile that endows bud cells with regenerative competence. Notably, the activation of this Piezo1-Yap1 mechanosensitive cascade in nonregenerative contexts is sufficient to induce the formation of competent bud-like structures, which are sufficient to drive de novo regeneration in these otherwise incompetent tissues. Taken together, our results reveal a mechanical state at the boundary between wound healing and regenerative bud formation, which is essential for synchronizing the transition between these pivotal stages of regeneration. More broadly, these findings support the general idea that the physical properties of tissues integrate with molecular frameworks to actuate cell state transitions during morphogenesis.

developmental biology↗

bioRxiv2024

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↗

bioRxiv2021

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↗