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Conserved Nuclear Morphology Identifies Functional Radial Glia Neural Progenitors

Soriano, J. P.; Borau, C.; Sortino, R.; Garma, L.; Ortega, J. A.; Asin, J.; Alcantara, S.

2025-01-09 developmental biology
10.1101/2025.01.09.632137 bioRxiv
Show abstract

Radial glia (RG) bipolar morphology is crucial for maintaining their integrity and function as neural stem cell and substrate for neural migration in the embryonic brain. We previously described that astrocytes dedifferentiate into functional RG when cultured on a RG mimetic micro3D platform, although we ignore the underlying mechanotransducive effectors. Here we analyzed the role of nuclear deformation to unravel their mechanotransducive effectors on RG induction. A multivariate generalized linear model developed for fitting RG identity probability revealed the existence of intrinsic nuclear constraints that allow a precise range of permitted RG nuclear morphologies, which are associated with particular nuclear calcium dynamics. Interestingly, RG nuclear constraints are conserved in vivo, in vitro and through evolution. Our work provides a framework for studying the interplay between nuclear mechanics, morphology, and cell fate decisions, offering a novel approach for RG identification and differentiation studies.

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