CONSERVED NUCLEAR MORPHOLOGY IDENTIFIES FUNCTIONAL RADIAL GLIA NEURAL PROGENITORS

Radial glia (RG) progenitor cells are the principal neural progenitors of the embryonic brain, giving rise to neurons and glial cells. RG apical-basal polarity and anchorage are crucial for maintaining their integrity and function. By using a biomimetic substrate that reproduces RG surface properties and mechanical anisotropy, we previously described the dedifferentiation of cultured astrocytes into functional RG, although the underlying mechanotransducive components remain largely unknown. Here we analyzed the role of nuclear morphology in mechanically driven RG induction, as nuclear deformation is critical for driving gene expression and cell fate changes in response to mechanical signals. A multivariate logistic regression model developed for fitting RG probability revealed the existence of intrinsic nuclear constraints, allowing a precise range of permitted RG nuclear morphologies, which are associated with calcium dynamics and conserved in vivo , in vitro and through evolution. Moreover, nuclear deformation predicts astrocyte or RG fate acquisition in response to mechanical signals.