Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain

• Published in: Scientific reports Vol. 6; no. 1; p. 19274
• Main Authors: Chou, Shen-Ju, Wang, Chindi, Sintupisut, Nardnisa, Niou, Zhen-Xian, Lin, Chih-Hsu, Li, Ker-Chau, Yeang, Chen-Hsiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.01.2016; Nature Publishing Group
• Subjects: 631/114/1314; 631/114/2404; Animals; Basal ganglia; Brain; Brain - metabolism; Cluster Analysis; Computational Biology; Computational neuroscience; Dopamine; Embryos; Forebrain; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Expression Regulation, Developmental; Humanities and Social Sciences; LIM-Homeodomain Proteins - deficiency; Mice; Mice, Knockout; multidisciplinary; Rodents; Science; Transcription Factors - deficiency; Transcriptome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep19274

Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.