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Transcript co-variance with Nestin in two mouse genetic reference populations identifies Lef1 as a novel candidate regulator of neural precursor cell proliferation in the adult hippocampus.

Ashbrook DG, Delprato A, Grellmann C, Klein M, Wetzel R, Overall RW, Badea A - Front Neurosci (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Computational and Evolutionary Biology, Faculty of Life Sciences, The University of Manchester Manchester, UK.

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.

No MeSH data available.


Expression of the six candidate genes in the hippocampus. Immunohistochemistry (ISH) is presented in the left column, the expression in the same sagittal slices in the right column. An atlas is shown above to help orientation. All images are taken from the Allen Mouse brain data (Lein et al., 2007; Allen Institute for Brain Science, 2014; http://www.brain-map.org).
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Figure 2: Expression of the six candidate genes in the hippocampus. Immunohistochemistry (ISH) is presented in the left column, the expression in the same sagittal slices in the right column. An atlas is shown above to help orientation. All images are taken from the Allen Mouse brain data (Lein et al., 2007; Allen Institute for Brain Science, 2014; http://www.brain-map.org).

Mentions: A differential search was performed using the Allen Brain Atlas Resource which produced a list of 2472 genes with enhanced expression in the hippocampal dentate gyrus, contrasted against the whole gray matter of the brain. This was used to narrow the list of 144 genes obtained through correlation with our Nes-PC1 meta-trait down to six candidate genes (Figure 1D). These candidates, correlating with Nes and enriched in the dentate gyrus, are therefore hypothesized to be involved in adult hippocampal neurogenesis. The six candidates are: Amer3 (Fam123c), Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1. The ISH data and expression intensity for these 6 genes are presented in Figure 2.


Transcript co-variance with Nestin in two mouse genetic reference populations identifies Lef1 as a novel candidate regulator of neural precursor cell proliferation in the adult hippocampus.

Ashbrook DG, Delprato A, Grellmann C, Klein M, Wetzel R, Overall RW, Badea A - Front Neurosci (2014)

Expression of the six candidate genes in the hippocampus. Immunohistochemistry (ISH) is presented in the left column, the expression in the same sagittal slices in the right column. An atlas is shown above to help orientation. All images are taken from the Allen Mouse brain data (Lein et al., 2007; Allen Institute for Brain Science, 2014; http://www.brain-map.org).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264481&req=5

Figure 2: Expression of the six candidate genes in the hippocampus. Immunohistochemistry (ISH) is presented in the left column, the expression in the same sagittal slices in the right column. An atlas is shown above to help orientation. All images are taken from the Allen Mouse brain data (Lein et al., 2007; Allen Institute for Brain Science, 2014; http://www.brain-map.org).
Mentions: A differential search was performed using the Allen Brain Atlas Resource which produced a list of 2472 genes with enhanced expression in the hippocampal dentate gyrus, contrasted against the whole gray matter of the brain. This was used to narrow the list of 144 genes obtained through correlation with our Nes-PC1 meta-trait down to six candidate genes (Figure 1D). These candidates, correlating with Nes and enriched in the dentate gyrus, are therefore hypothesized to be involved in adult hippocampal neurogenesis. The six candidates are: Amer3 (Fam123c), Eya3, Mtdh, Nr4a3, Polr2a, and Tbkbp1. The ISH data and expression intensity for these 6 genes are presented in Figure 2.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Computational and Evolutionary Biology, Faculty of Life Sciences, The University of Manchester Manchester, UK.

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.

No MeSH data available.