Afadin Loss Uncovers an Ectopic Neurogenic Niche and Reorganizes the Adult Ventricular-Subventricular Zone

Neural stem cells (NSCs) sustain neurogenesis within specialized niches, yet how adhesion-dependent mechanisms during development control lifelong behavior remains unclear. Here, we identify Afadin , a core adherens junction protein, as a regulator. Dorsal loss of Afadin during development drives formation of a stable, ventricular-independent ectopic germinal zone in the neocortex, populated by self-renewing, multipotent NSCs sustaining neurogenesis into adulthood. This ectopic niche emerges within a disorganized cortical environment reminiscent of subcortical band heterotopia, a malformation linked to human neurodevelopmental disorders. Concomitantly, the canonical ventricular-subventricular zone (V-SVZ) is disrupted, with persistent NSC activation, altered ependymal specification, ventricular disorganization, and increased neurogenesis. Transcriptomic profiling of the V-SVZ reveals a shift from adhesion- and quiescence-associated programs toward proliferative and neurogenic states through cell-autonomous and non-cell-autonomous mechanisms. Mosaic postnatal or adult deletion confirms a cell-intrinsic role of Afadin in NSC activation. Together, these findings reveal flexibility and plasticity of NSCs across the lifespan.