Abstract
Adult neurogenesis, the lifelong production of new neurons in the adult brain, is under complex genetic control but many of the genes involved remain to be identified. In this study, we have integrated publicly available gene expression data from the BXD and CXB recombinant inbred mouse lines to discover genes co-expressed in the adult hippocampus with Nestin, a common marker of the neural precursor cell population. In addition, we incorporated spatial expression information to restrict candidates to genes with high differential gene expression in the hippocampal dentate gyrus. Incorporating data from curated protein-protein interaction databases revealed interactions between our candidate genes and those already known to be involved in adult neurogenesis. Enrichment analysis suggested a link to the Wnt/β-catenin pathway, known to be involved in adult neurogenesis. In particular, our candidates were enriched in targets of Lef1, a modulator of the Wnt pathway. In conclusion, our combination of bioinformatics approaches identified six novel candidate genes involved in adult neurogenesis; Amer3, Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1. Further, we propose a role for Lef1 transcriptional control in the regulation of adult hippocampal precursor cell proliferation.
Highlights
In the hippocampal dentate gyrus of many mammalian species, including mice (Kempermann et al, 1997a,b) and humans (Eriksson et al, 1998), there exists a population of neural stem cells that continue to divide and give rise to new granule cell neurons throughout adulthood
The results presented above support the hypothesis that Lef1 plays a gene regulatory role in type-1 and type-2 Nestin-positive cells in the adult hippocampal dentate gyrus
Adult neurogenesis occurs in several mammalian species, the rate of precursor proliferation and new neuron production vary considerably between species (Kempermann, 2012)
Summary
In the hippocampal dentate gyrus of many mammalian species, including mice (Kempermann et al, 1997a,b) and humans (Eriksson et al, 1998), there exists a population of neural stem cells that continue to divide and give rise to new granule cell neurons throughout adulthood The proliferation of these precursor cells is under strong genetic control (Kempermann et al, 1997a, 2006; Kempermann and Gage, 2002); and is modulated by a complex interplay of genetic interactions (Kempermann et al, 2006; Pozniak and Pleasure, 2006; Kempermann, 2011). We identified two such resources for which compatible hippocampal expression data exist (Overall et al, 2009): the BXD RI cross between C57BL/6J and DBA/2J (Taylor, 1978; Taylor et al, 1999; Peirce et al, 2004), and the CXB RI cross between C57BL/6ByJ and BALB/cByJ (Bailey, 1971; Nowakowski, 1984)
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