Microtubules and nuclear pores position centromeres and genes in neural stem cells

Chromatin’s spatial organization is important for cell division, epigenetic memory, and gene regulation. Chromatin architecture is often reflected in nonrandom centromere positioning, which changes during development and disease. However, the mechanisms and functions of centromere positioning remain largely unknown. Here, we report that Drosophila neural stem cells cluster centromeres near the nuclear envelope, adjacent to the apical centrosome. This asymmetric centromere positioning persists throughout interphase but is lost in differentiated progeny. Asymmetric centromere positioning is regulated by microtubules from the apical centrosome connected to nuclear pore complexes (NPCs), generating a pulling force mediated by the motor protein Dynein and its binding partner Mushroom body defect. Lamin facilitates centromere–NPC binding, necessary for centromere positioning and clustering. We also find that the developmentally regulated genes hunchback and pendulin occupy specific nuclear regions, correlating with polarized centromere localization. We propose that fly neural stem cells translate their inherent polarity into stereotypical chromatin organization, potentially influencing cell-fate decisions and stem cell behavior.