Developmental remodeling uncouples neural stem cell function from niche anatomy

Abstract

Stem cells are generally thought to depend on specialized niches that provide signals for their long-term maintenance. Whether stem-cell competence is intrinsically constrained by anatomical organization remains unclear. Here, we show that neural stem cells can establish and sustain functional persistent stem-cell populations outside their normal anatomical context. Using developmental deletion of the cell-adhesion regulator Afadin as a tool to disrupt cortical tissue organization, we find that neural progenitors are displaced from the ventricular surface and establish an ectopic germinal zone (EGZ) into advanced adulthood. EGZ stem-cell populations retain self-renewal and multilineage differentiation capacity throughout this period. In parallel, the ventricular-subventricular zone (V-SVZ) undergoes persistent reorganization of tissue architecture, cellular composition, molecular state, and stem-cell activity. Together, these findings reveal unexpected plasticity in the relationship between stem cells and their tissue environment, suggesting that canonical niche anatomy may constrain where stem cells normally reside without defining the limits of functional stem-cell competence.