Grant: Discovery Grants Program - Individual

There are several significant gaps in our understanding of central nervous system (CNS) development. It is widely understood that pools of neural precursor cells (NPC; a more mature stem cell) can develop and mature into different cell types of the nervous system (e.g. neurons and supportive cells) in both the immature and mature mammal. However the cellular signaling required to mediate these changes and the effect of environmental oxygen has on this maturation process have not been fully investigated. Studies suggest that various released factors, in the developing CNS, initiate the maturation and migration of NPC from distant sources. Little is known as to the source of these factors, in addition to how they are released (always released or stimulated release). The second aim of these studies is to investigate the role of different oxygen environments may have on NPC development. Often research in stem cell biology uses atmospheric oxygen (21% oxygen) or anoxia (<0% oxygen) in the study of precursor cell development. In comparison to the environment that these cells or tissue are normally exposed to, atmospheric oxygen is hyperoxic (high oxygen levels). For example in the developing fetus, arterial oxygen levels are in the range of (5-8% oxygen). Although arterial oxygen levels are higher in the mature mammal, it is still lower than that used in most studies. Oxygen may modulate cellular behavior via activation of protein signaling pathways or activation of membrane ion channels that control cellular excitability and the influx of calcium and other ions. Since activation of these proteins and ion channels typically occurs over specific concentrations of oxygen, it is important to understand the effects of physiologically relevant oxygen levels have on neural precursor cell development. This will help improve our understanding of CNS development in addition to the remodeling pathways that occur in the mature nervous system.