BMP signaling regulates the tempo of adult hippocampal progenitor maturation at multiple stages of the lineage.

Novel environmental stimuli, such as running and learning, increase proliferation of adult hippocampal neural stem cells (NSCs) and enlarge the population of new neurons. However, it remains unclear how increased numbers of new neurons can be generated in a time frame far shorter than the time required for proliferating stem cells to generate these neurons. Here, we show that bone morphogenetic protein (BMP) signaling in the subgranular zone regulates the tempo of neural progenitor cell (NPC) maturation by directing their transition between states of quiescence and activation at multiple stages along the lineage. Virally mediated overexpression of BMP4 caused NPC cell cycle exit and slowed the normal maturation of NPCs, resulting in a long-term reduction in neurogenesis. Conversely, overexpression of the BMP inhibitor noggin promoted NPC cell cycle entry and accelerated NPC maturation. Similarly, BMP receptor type 2 (BMPRII) ablation in Ascl1(+) intermediate NPCs accelerated their maturation into neurons. Importantly, ablation of BMPRII in GFAP(+) stem cells accelerated maturation without depleting the NSC pool, indicating that an increased rate of neurogenesis does not necessarily diminish the stem cell population. Thus, inhibition of BMP signaling is a mechanism for rapidly expanding the pool of new neurons in the adult hippocampus by tipping the balance between quiescence/activation of NPCs and accelerating the rate at which they mature into neurons.

Synthetic Polymers Provide a Robust Substrate for Functional Neuron Culture.

Substrates for neuron culture and implantation are required to be both biocompatible and display surface compositions that support cell attachment, growth, differentiation, and neural activity. Laminin, a naturally occurring extracellular matrix protein is the most widely used substrate for neuron culture and fulfills some of these requirements, however, it is expensive, unstable (compared to synthetic materials), and prone to batch-to-batch variation. This study uses a high-throughput polymer screening approach to identify synthetic polymers that supports the in vitro culture of primary mouse cerebellar neurons. This allows the identification of materials that enable primary cell attachment with high viability even under "serum-free" conditions, with materials that support both primary cells and neural progenitor cell attachment with high levels of neuronal biomarker expression, while promoting progenitor cell maturation to neurons.