Centrioles and Cellular Differentiation
Jaba Tkemaladze
Abstract
For decades, centrioles have been studied primarily for their canonical roles in organizing the mitotic spindle and templating cilia. However, a paradigm shift is underway. This meta-analysis synthesizes contemporary evidence to argue that centrioles are, in fact, pivotal regulatory hubs that directly govern cellular differentiation and fate specification. Moving beyond their structural functions, centrioles influence differentiation through a multi-faceted framework: (1) by ensuring precise spindle geometry and orientation to execute asymmetric cell divisions that segregate fate determinants; (2) by serving as the mandatory platform for the primary cilium, a signaling compartment essential for transducing Hedgehog, Wnt, and other developmental pathways; (3) by acting as sensors of homeostatic integrity, where aberrations in their number or structure trigger p53-dependent signaling to influence cell cycle exit and differentiation; and (4) by modulating cellular competence through "centrosomal maturity," which dictates cytoskeletal polarization and responsiveness to differentiation cues. This integrative role resolves the apparent paradox of an organelle central to cell division being crucial for post-mitotic specialization. The findings redefine centrioles as dynamic information processors, linking their dysfunction to developmental centriolopathies and cancer, and positing them as novel targets for controlling stem cell fate in regenerative medicine.