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Date and Time 2007-04-11 14:45:00 - 15:45:00
Venue Seminar Room A7F
Speaker Hiroshi Asahara
National Research Institute for Child Health and Development
Title TRANSCRIPTIONAL NETWORK REGULATING LIMB DEVELOPMENT
Host Takayuki Asahara
Summary Sox9, high-mobility group (HMG)-box domain transcription factor, is known to play an essential role in initiating morphogenesis via chondroblast differentiation by regulating the transcription of type II collagen gene (Col2a1). To understand transcriptional network anchored by Sox9 during limb development, we combined three different post-genomic approaches and subsequently proved them by mice gene targeting experiments; (1) To examine the spatio-temporal expression patterns of nuclear factors (NFs; including transcription factors (TFs) and cofactors) regulating limb development, we performed whole-mount in situ hybridization (WISH) for more than 1,600 of mouse NFs systematically and successfully developed WISH database using mouse E9.5, 10.5, and 11.5 embryos. Based on this database, we identified NFs cluster which show the same expression pattern with Sox9. (2) To examine the direct targets of Sox9, we performed Chip-on-Chip assay and identified several novel Sox9 downstream targets. (3) To analyze molecules which promote chondrogenesis via Sox9 activation, we performed cell based high-through put transfection assay for 16,000 genes and determined novel molecular signals which promote Sox9 activity. Using knock-out mice, we showed that these factors in the Sox9 network cooperatively promote chondrogenesis and limb development, suggesting that our combined post-genomic approaches are powerful tools to identify critical gene clusters for tissue and organ development.
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