1Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 2Departamento de Biología Celular, Biología Funcional y Antropología Física, 3Instituto de Biotecnología y Biomedicina (BioTecMed), Universidad de Valencia, 46100 Burjassot, Spain.

New neurons for highly plastic olfactory circuits are produced in the subependymal zone (SEZ) of the adult mammalian brain. Neural stem cells (NSCs) in this niche have access to a wide range of regulatory signals that promote continuous lifelong neurogenesis while preserving the stem cell pool. NSCs derive from radial glial cells, which are the primary embryonic progenitor type in the vertebrate brain, and inherit from them part of their transcriptional program, a bipolar elongated morphology with apico-basal polarity that allows for unique interactions with neighboring cell types, and markers associated with the astrocytic lineage. In contrast to their fetal counterparts, most adult NSCs remain in a quiescent state under physiological conditions. It is now widely accepted that NSCs in the SEZ exist in at least three states: quiescent (q), quiescent but prone to activation or primed (p), and activated (a), each characterized by unique and distinct transcriptional profiles. Transitions between states likely involve significant changes in cellular physiology tightly regulated by both intrinsic and extrinsic factors. We have found that entry into quiescence is associated with the deposition of specific extracellular matrix components and that adhesion to the matrix produced in response to pro-quiescent signals alone can induced a quiescent-like state in proliferative NSCs. This entry into quiescence depends on the RhoA-associated kinase ROCK and yes-associated protein (YAP) transcriptional activity. YAP/TAZ deletion in NSCs leads to the loss of ECM deposition and quiescence in vivo suggesting that they regulate the physical niche and a quiescence-associated gene expression program in response to mechanical cues.