Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing

Abstract

Brain structure and function experience dramatic changes from embryonic to postnatal development. Microarray analyses have detected differential gene expression at different stages and in disease models, but gene expression information during early brain development is limited. We have generated >27 million reads to identify mRNAs from the mouse cortex for >16,000 genes at either embryonic day 18 (E18) or postnatal day 7 (P7), a period of significant synaptogenesis for neural circuit formation. In addition, we devised strategies to detect alternative splice forms and uncovered more splice variants. We observed differential expression of 3,758 genes between the 2 stages, many with known functions or predicted to be important for neural development. Neurogenesis-related genes, such as those encoding Sox4, Sox11, and zinc-finger proteins, were more highly expressed at E18 than at P7. In contrast, the genes encoding synaptic proteins such as synaptotagmin, complexin 2, and syntaxin were up-regulated from E18 to P7. We also found that several neurological disorder-related genes were highly expressed at E18. Our transcriptome analysis may serve as a blueprint for gene expression pattern and provide functional clues of previously unknown genes and disease-related genes during early brain development.E18 ͉ P7 ͉ brain ͉ transcription factors ͉ neural diseases M ammalian brain development can be largely divided into 2 periods: embryonic and postnatal. Embryonic mouse brain development starts Ϸ10-11 days after gestation (E10-E11) with massive neuronal production from neural stem cells. The development of rodent cerebral cortex is a well-studied model system, where the initial neurons form the subplate layer, although subsequent neurons migrate in an inside-out pattern to form the multilayer cortical structure (1, 2). By embryonic day 18 (E18), neurons start to send out axons and dendrites to be poised for synaptic connections. After birth, the first week of postnatal brain development is characterized by elevated production of astrocytes, which are crucial for neuronal synaptogenesis (3, 4). By postnatal day 7, many neurons start to establish synaptic connections with other neurons, forming a primitive neural circuit. Early brain development is precisely controlled by transcription factors, cell adhesion molecules, receptors and channels, synaptic proteins, and other effectors. A single misstep might result in a severe deformation of the brain circuit. For example, loss of Otx2 function results in the absence of early brain development (5). Since many psychiatric disorders such as autism and mental retardation are closely associated with early brain development, understanding the gene expression profile will facilitate the search for an optimal treatment for these disorders. Previous surveys of early brain development have focused on a small number of genes. More recently, microarray studies and others have revealed differential expression of groups of genes in specific brain regions or associated with brain disorders (6-1...

Expression and localization of Inter-alpha Inhibitors in rodent brain

“…Embryonic and postnatal stages are the most important periods of mammalian brain development (Han et al, 2009). Neuronal development is established by E18 in mouse brain (Han et al, 2009, Watkins et al, 2012).…”

“…Neuronal development is established by E18 in mouse brain (Han et al, 2009, Watkins et al, 2012). Therefore, we investigated the expression of IAIPs in neurons with immunohistochemical staining using Fox3/NeuN as a neuronal marker in the cerebral cortex and in the hippocampus of the E18 mouse brain (Figs.…”

De novo assembly and characterization of the spleen transcriptome of common carp (Cyprinus carpio) using Illumina paired-end sequencing

“…Recently, rapid developments in high-throughput deep sequencing technologies have provided a powerful platform for the rapid and nearly complete characterization of transcriptomic events in various species [14,15]. De novo transcriptome sequencing has become an important method for studying non-model organisms [8,16].…”

Transcriptional programs in transient embryonic zones of the cerebral cortex defined by high-resolution mRNA sequencing

“…Whole-transcriptome mRNA sequencing (mRNA-seq) is a breakthrough technology that provides quantitative and sensitive detection with a broad dynamic range (17), which was recently demonstrated by Han and colleagues (18). This study described global gene and alternative isoform expression using mRNA-seq on mouse neocortex at late embryonic (embryonic day [E] 18) and early postnatal (postnatal day [P] 7) ages.…”