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Borau, C.

Publications and source records attributed to Borau, C..

2 recordsLinked to original sources

CONSERVED NUCLEAR MORPHOLOGY IDENTIFIES FUNCTIONAL RADIAL GLIA NEURAL PROGENITORS

Mechanical cues influence neural development, yet how tissue architecture is integrated into progenitor cell states remains poorly understood. Here, we show that defined microtopographies induce an early nuclear remodeling program associated with radial glia (RG)-like competence. Aligned microgrooves promote nuclear elongation, reduced Lamin A/C to B1 ratio, sustained {beta}-catenin activity, and distinct patterns of nuclear calcium dynamics, all of which merge before peak Pax6 expression. Pharmacological inhibition of mechanosensitive calcium signaling abolishes RG-associated marker induction while preserving nuclear remodeling, indicating that calcium-dependent pathways are required for Pax6 induction but are dispensable for the establishment of the underlying morphometric state. To quantitatively describe these transitions, we developed an interpretable model based on nuclear geometry and local cell density that identifies morphometric states associated with RG-like competence across experimental conditions. Application of this framework to embryonic mouse and human cortex revealed analogous signatures in native RG populations. Together, these findings indicate that tissue architecture influences RG-like competence through conserved nuclear morphometric states across developmental contexts.

developmental biology↗

Brain tissue mechanics is governed by microscale relations of the tissue constituents

Local mechanical tissue properties are a critical regulator of cell function in the central nervous system (CNS) during development and disorder. However, we still dont fully understand how the mechanical properties of individual tissue constituents, such as cell nuclei or myelin, determine tissue mechanics. Here we developed a model predicting local tissue mechanics, which induces non-affine deformations of the tissue components. Using the mouse hippocampus and cerebellum as model systems, we show that considering individual tissue components alone, as identified by immunohistochemistry, is not sufficient to reproduce the local mechanical properties of CNS tissue. Our results suggest that brain tissue shows a universal response to applied forces that depends not only on the amount and stiffness of the individual tissue constituents but also on the way how they assemble. Our model may unify current incongruences between the mechanics of soft biological tissues and the underlying constituents and facilitate the design of better biomedical materials and engineered tissues. To this end, we provide a freely-available platform to predict local tissue elasticity upon providing immunohistochemistry images and stiffness values for the constituents of the tissue.

biophysics↗