, 2006). However, none of the RI strains had more cells than C57BL/6J, but more than half of the RI strains had fewer cells than in A/J (Fig. 7A). Genetic analysis using QTL interval mapping of the SGZ phenotype showed that one suggestive QTL modulated the number of proliferating SGZ cells was located on Chr 3 at 102 ± 7 Mb (genome-wide P < 0.63; LRS = 12.79; LOD = 2.77) (Fig. 7B and C). We also found that having an A allele in the QTL 3 interval Proteasome inhibitor was associated with an increase of 5 BrdU+ cells/mm in SGZ cellular proliferation when compared with RI strains with the B allele (Fig. 7C). This SGZ QTL does not correspond to those seen for the RMS, suggesting that the RMS and SGZ have region-specific molecular

mechanisms for controlling adult neurogenesis. In this study, we identified a robust QTL associated with variation in RMS cellular proliferation on mouse chromosome 11, which is syntenic with human chromosome 17q25.1. We named this novel QTL Rmspq1 and there are two prominent features of this QTL: (1) it is centered at 116.75Mb on chromosome 11, and (2) selleck compound it is 1.5 Mb wide as defined by the 2.0- LOD support confidence interval. A total of 36 genes, 25 known and 11 predicted, reside in this QTL interval (Table 1). Of all the genes examined, two met all our three candidate gene criteria (see Materials and methods) and are considered as priority genes for future analysis. One of them is sphingosine

kinase 1 (Sphk1), which is expressed in adult murine brain and has been implicated in cellular processes including cell proliferation and cell survival (Kohama et al., 1998; Hait et al., 2006). One major role of Sphk1 is to generate Sphingosine-1-phosphate (S1P) from its metabolic precursor sphingosine, and S1P is a lipid second messenger that plays an important role in both vasculogenesis and neurogenesis (Harada et al., 2004; Mizugishi et al., 2005). Our pathway analysis using DAVID (http://david.abcc.ncifcrf.gov:8080/)

showed Sphk1 is part of the vascular endothelial growth factor (VEGF) signaling Bay 11-7085 pathway that when activated increases proliferation in the SVZ and also modulates migration of the neural progenitors in the RMS (Wittko et al., 2009). There are three Single Nucleotide Polymorphisms (SNPs) identified when comparing the A/J and C57BL/6J genome at the Gene Network’s variant browser. One is a synonymous SNP located in exon 5, while the remaining two SNPs – one located in intron 2 and the other in intron 5 – have unknown functions. Another gene, the galanin receptor 2 (Galr2), also emerged as a strong candidate gene that may control the number of proliferating cells in the RMS. Galr2 is the receptor for galanin, a neuropeptide involved in mood regulation that is expressed throughout the brain including SVZ, RMS and DG (Ma et al., 2008). Activation of Galr2 through the binding of galanin has been linked to increased hippocampal neurogenesis in the seizure-induced injured brain (Mazarati et al., 2004).