, 2010). Wnt and Hh morphogens play essential and sometimes opposing roles in development of the central nervous system and can act to affect both proliferation and cell fate (reviewed in Rowitch et al., 1997, Fuccillo et al., 2006 and Ulloa and Briscoe, 2007). Both pathways are also active in the adult VZ-SVZ and affect self-renewal, proliferation, find more and migration, as discussed above. To date, it is unknown whether these two pathways

interact functionally in this context. It is possible that Wnt may act in concert with FGF signaling and/or in opposition to Shh signaling, as is the case in early nervous system development (Ulloa et al., 2007 and Alvarez-Medina et al., 2008). Going forward,

it will be fascinating to understand how the many growth factor and morphogen-driven pathways active in the SVZ are functionally integrated to affect progenitor proliferation and differentiation. With some exceptions noted above, most of these pathways have been examined in isolation, and determining PI3K Inhibitor Library how these pathways interact will be essential to understanding the normal regulation of neurogenesis. In addition to the wealth of extracellular signaling pathways that are thought to act within the adult VZ-SVZ, intracellular actors, including transcription factors, nuclear receptors, chromatin-modifying complexes, and microRNAs, have been reported to affect the neural stem cell lineage. The transcription factors Dlx2, Mash1, and NeuroD1 are all associated with a neurogenic fate, while Olig2 is primarily gliogenic (Parras et al., 2004, Hack et al., aminophylline 2005, Marshall et al., 2005, Menn et al., 2006, Petryniak et al., 2007 and Gao et al., 2009). However, it is still unclear how niche-provided signals and subsequent intracellular signaling cascades ultimately result in the expression of specific neurogenic or gliogenic transcription factors. Recent work has highlighted the essential role of

epigenetic regulators such as the chromatin-modifying protein Mll1 and the microRNA miR-124 in the control of neurogenesis (Lim et al., 2006, Lim et al., 2009 and Cheng et al., 2009). The orphan nuclear receptor Tlx is also required for neural stem cell self-renewal and may mediate the repression of cell cycle inhibitory factors through the recruitment of Bmi-1 (Sun et al., 2007, Liu et al., 2008 and Liu et al., 2010). The expression of epigenetic regulators like Bmi-1 is altered as the organism ages and stem cell function declines (Molofsky et al., 2003, Molofsky et al., 2006 and Fasano et al., 2009). Although Mll1 and Bmi-1 are broadly expressed within the VZ-SVZ lineage, both proteins appear to function at specific points in this lineage to permit division or neurogenesis.