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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, D. G., Delprato, A., Grellmann, C., Klein, M., Wetzel, R., Overall, R. W., et al. (2014). 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. Frontiers in Neuroscience, 8: 418. doi:10.3389/fnins.2014.00418.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-0B92-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-7C3A-2
Genre: Journal Article

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 Creators:
Ashbrook, David G.1, Author
Delprato, Anna2, 3, Author
Grellmann, Claudia4, 5, Author              
Klein, Marieke6, Author
Wetzel, Richard7, Author
Overall, Rupert W.8, Author
Badea, Alexandra9, Author
Affiliations:
1Computational and Evolutionary Biology, Faculty of Life Sciences, University of Manchester, United Kingdom, ou_persistent22              
2BioScience Project, Wakefield, MA, USA, ou_persistent22              
3Institut de Neurosciences cognitives et intégratives d'Aquitaine, Université de Bordeaux, France, ou_persistent22              
4Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              
5Integrated Research and Treatment Center Adiposity Diseases, University of Leipzig, Germany, ou_persistent22              
6Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands, ou_persistent22              
7German Center for Neurodegenerative Diseases, Dresden, Germany, ou_persistent22              
8Genomics of Regeneration Group, Center for Regenerative Therapies Dresden, TU Dresden, Germany, ou_persistent22              
9Department of Radiology, Center for In Vivo Microscopy, Duke University School of Medicine, Durham, NC, USA, ou_persistent22              

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Free keywords: Adult neurogenesis; BXD; CXB; Neuroinformatics; Recombinant inbred mice; Systems genetics; Lef1; Wnt pathway
 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.

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Language(s): eng - English
 Dates: 2014-09-192014-11-272014-12-12
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.3389/fnins.2014.00418
PMID: 25565948
PMC: PMC4264481
Other: eCollection 2014
 Degree: -

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Title: Frontiers in Neuroscience
  Other : Front Neurosci
Source Genre: Journal
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Publ. Info: Lausanne, Switzerland : Frontiers Research Foundation
Pages: - Volume / Issue: 8 Sequence Number: 418 Start / End Page: - Identifier: ISSN: 1662-4548
ISSN: 1662-453X
CoNE: https://pure.mpg.de/cone/journals/resource/1662-4548