Developmental cues and persistent neurogenic potential within an in vitro neural niche

We describe a model in vitro NSC niche, derived from embryonic stem cells, that produces many of the cells and products of the developing subventricular zone (SVZ) and adult SEZ NSC niche. We demonstrate a possible role for apoptosis and for components of the extracellular matrix in the maintenance of the NSC population within our niche cultures. We characterize expression of genes relevant to NSC self-renewal and the process of neurogenesis and compare these findings to gene expression produced by an established neural-induction protocol employing retinoic acid.The in vitro NSC niche shows an identity that is distinct from the neurally induced embryonic cells that were used to derive it. Molecular and cellular components found in our in vitro NSC niche include NSCs, neural progeny, and ECM components and their receptors. Establishment of the in vitro NSC niche occurs in conjunction with apoptosis. Applications of this culture system range from studies of signaling events fundamental to niche formation and maintenance as well as development of unique NSC transplant platforms to treat disease or injury.The mammalian brain contains a NSC niche that produces neurons and glia for the developing (within the SVZ) and adult (within the SEZ) brain [1-9]. This niche consists of NSCs, their progeny (transit amplifying cells and neuroblasts), ependymal cells, a basal lamina and complex extracellular matrix (ECM), and a microenvironment consisting of factors provided by cells within the niche and adjacent blood vessels [1,3,4,6,8-14]. The function of the niche is to produce new neurons and glia during development and to supply replacement cells due to turnover in the olfactory bulb and in response to disease or injury in the central nervous system [1-9]. Recent classification of an intermediate progenitor adjacent to the ventricular zone has made the nomenclature of neural stem and progenitor cells and respective niches more complex [15,16]. Reference to related literature is h