, 2007, Dranovsky and selleck Hen, 2006, Malberg et al., 2000, Stranahan et al., 2006 and van Praag et al., 1999). Adult-born neurons have been causally implicated in specific cognitive and emotional functions (Leuner et al., 2006, Sahay and Hen, 2007 and Zhao et al., 2008), and several recent studies have begun to delineate a role for adult

hippocampal neurogenesis within normal hippocampal physiology (Clelland et al., 2009, Kitamura et al., 2009, Sahay et al., 2011 and Saxe et al., 2006). However, the extent to which adult-born neurons contribute to normal brain function remains controversial because their contribution to hippocampal structure remains unclear (Breunig et al., 2007). Adult-born neurons are thought to differentiate

from radial astrocyte-like neural stem cells (NSCs) Selleck Z-VAD-FMK via an intermediate multipotent neuronal progenitor (IP) and become integrated into existing networks (Carlén et al., 2002, Laplagne et al., 2006, Seri et al., 2004, Toni et al., 2008 and van Praag et al., 2002). Adult NSCs are currently thought to be a slowly dividing, relatively quiescent reservoir (Encinas et al., 2006), although this notion is beginning to be challenged (Lugert et al., 2010). Mitotic cell label retention studies suggest that some adult-born neurons persist for the life of the animal (Dayer et al., 2003 and Doetsch and Hen, 2005). However, mitotic label retention is not informative about populations of cells since a decrease in labeled cells can represent either cell death or label dilution that accompanies increased division (Breunig et al., 2007). Unlike label retention studies, indelible lineage analysis is a cumulative assessment of cellular populations derived from genetically defined stem cells. Such populations are a summation of the birth and death of all cells within the NSC-derived

lineage. Hence, indelible lineage analyses have been successfully used to examine tissue homeostasis Carnitine palmitoyltransferase II (Morrison and Spradling, 2008). Some indelible lineage studies have been carried out looking at the adult hippocampus (Ahn and Joyner, 2005, Imayoshi et al., 2008, Lagace et al., 2007 and Li et al., 2008). However, the results have been widely variable since sensitivity of cellular proliferation to environmental changes renders even subtle experimental differences to manifest in increasingly pronounced changes as the lineage expands over time. Such changes would be especially profound if experimental differences affected the specification of stem cell fate, since directing stem cell fate results in altering the trajectory of the entire derived lineage.