Research

Molecular networks involved in mouse cerebral corticogenesis and spatio-temporal regulation of Sox4 and Sox11 novel antisense transcripts revealed by transcriptome profiling

King-Hwa Ling^1,2,3,7 , Chelsee A Hewitt^1,9 , Tim Beissbarth^4,10 , Lavinia Hyde^4,11 , Kakoli Banerjee⁵ , Pike-See Cheah^5,6 , Ping Z Cannon¹ , Christopher N Hahn⁷ , Paul Q Thomas⁵ , Gordon K Smyth⁴ , Seong-Seng Tan⁸ , Tim Thomas¹ and Hamish S Scott^1,2,7

¹  Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3052, Australia

²  The School of Medicine, The University of Adelaide, SA, 5005, Australia

³  Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia

⁴  Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3052, Australia

⁵  School of Molecular and Biomedical Science, Faculty of Sciences, University of Adelaide, Adelaide, SA 5005, Australia

⁶  Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor DE, Malaysia

⁷  Department of Molecular Pathology, The Institute of Medical and Veterinary Science and The Hanson Institute, Adelaide, SA 5000, Australia

⁸  Howard Florey Institute, The University of Melbourne, Parkville, Victoria 3010, Australia

⁹  Current address: Pathology Department, The Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia

¹⁰  Current address: Department of Medical Statistics (Biostatistics), University of Göttingen, Humboldtalle 32, 37073 Göttingen, Germany

¹¹  Current address: The Bioinformatics Unit, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria 3052, Australia

author email corresponding author email

Genome Biology 2009, 10:R104doi:10.1186/gb-2009-10-10-r104

Published:	2 October 2009

Subject areas: Development, Genome studies, Neurobiology

Abstract

Background

Development of the cerebral cortex requires highly specific spatio-temporal regulation of gene expression. It is proposed that transcriptome profiling of the cerebral cortex at various developmental time points or regions will reveal candidate genes and associated molecular pathways involved in cerebral corticogenesis.

Results

Serial analysis of gene expression (SAGE) libraries were constructed from C57BL/6 mouse cerebral cortices of age embryonic day (E) 15.5, E17.5, postnatal day (P) 1.5 and 4 to 6 months. Hierarchical clustering analysis of 561 differentially expressed transcripts showed regionalized, stage-specific and co-regulated expression profiles. SAGE expression profiles of 70 differentially expressed transcripts were validated using quantitative RT-PCR assays. Ingenuity pathway analyses of validated differentially expressed transcripts demonstrated that these transcripts possess distinctive functional properties related to various stages of cerebral corticogenesis and human neurological disorders. Genomic clustering analysis of the differentially expressed transcripts identified two highly transcribed genomic loci, Sox4 and Sox11, during embryonic cerebral corticogenesis. These loci feature unusual overlapping sense and antisense transcripts with alternative polyadenylation sites and differential expression. The Sox4 and Sox11 antisense transcripts were highly expressed in the brain compared to other mouse organs and are differentially expressed in both the proliferating and differentiating neural stem/progenitor cells and P19 (embryonal carcinoma) cells.

Conclusions

We report validated gene expression profiles that have implications for understanding the associations between differentially expressed transcripts, novel targets and related disorders pertaining to cerebral corticogenesis. The study reports, for the first time, spatio-temporally regulated Sox4 and Sox11 antisense transcripts in the brain, neural stem/progenitor cells and P19 cells, suggesting they have an important role in cerebral corticogenesis and neuronal/glial cell differentiation.