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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.


The integration of data from several online tools identifies a novel role for Lef1 in adult hippocampal neurogenesis. Enrichment analysis was carried out on the six candidate genes identified (Figure 1) and for targets of the transcription factor Lef1. This was further investigated using enrichment of genes known to be expressed in Nestin positive cells, correlation analysis between our candidate genes and Lef1, and the use of interaction databases to find links between our candidates.
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Figure 3: The integration of data from several online tools identifies a novel role for Lef1 in adult hippocampal neurogenesis. Enrichment analysis was carried out on the six candidate genes identified (Figure 1) and for targets of the transcription factor Lef1. This was further investigated using enrichment of genes known to be expressed in Nestin positive cells, correlation analysis between our candidate genes and Lef1, and the use of interaction databases to find links between our candidates.

Mentions: These enrichment analyses suggest a possible novel role of Lef1 as a key transcriptional regulator in proliferating neural precursor cells (Figure 3).


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)

The integration of data from several online tools identifies a novel role for Lef1 in adult hippocampal neurogenesis. Enrichment analysis was carried out on the six candidate genes identified (Figure 1) and for targets of the transcription factor Lef1. This was further investigated using enrichment of genes known to be expressed in Nestin positive cells, correlation analysis between our candidate genes and Lef1, and the use of interaction databases to find links between our candidates.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The integration of data from several online tools identifies a novel role for Lef1 in adult hippocampal neurogenesis. Enrichment analysis was carried out on the six candidate genes identified (Figure 1) and for targets of the transcription factor Lef1. This was further investigated using enrichment of genes known to be expressed in Nestin positive cells, correlation analysis between our candidate genes and Lef1, and the use of interaction databases to find links between our candidates.
Mentions: These enrichment analyses suggest a possible novel role of Lef1 as a key transcriptional regulator in proliferating neural precursor cells (Figure 3).

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.