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

Anna eDelprato¹  Alexandra eBadea²  Richard eWetzel³  Claudia eGrellmann⁵  Mareike eKlein⁶  Rupert W Overall⁷  David George Ashbrook⁸ 

[1] BioScience Project;Duke Univ Medical Center;German Center for Neurodegenerative Diseases (DZNE);Leipzig University Medical Center;Max Planck Institute for Human Cognitive and Brain Sciences;Radboud University Nijmegen Medical Centre, Donders Institute for Brain;Technische Universität Dresden;The University of Manchester,;

关键词: bioinformatics;    adult neurogenesis;    BXD;    neuroinformatics;    Systems genetics;    recombinant inbred mice;   

DOI  :  10.3389/fnins.2014.00418

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown