| Budget Amount *help |
¥51,740,000 (Direct Cost: ¥39,800,000、Indirect Cost: ¥11,940,000)
Fiscal Year 2006: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000)
Fiscal Year 2005: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
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| Research Abstract |
In this project, we have studied how future head is specified, induced and formed in the mouse embryo. In particular, the following four topics have been focus.
1. How the anterior-posterior polarity is determined: we have studied how DVE (distal visceral endoderm) is formed in pre-gastrulating embryo, and have revealed a role of BMP signal in DVE formation.
2. Role of Nodal signal in head formation: Nodal signaling, which plays a important role in head formation, is mediated by a transcription factor called FoxH1. To understand the mechanism of head formation by Nodal, we have systemically searched the mouse genome for genes regulated by FoxH1, and have identified about 150 candidate genes. We are now examining their expression patterns in the wild-type and FoxH1 mutant embryos. At least, some genes are genuine FoxH1-targets because their expression was impaired in the mutant embryo.
3. Regionalization of CNS by retinoic acid: we have studied the role of retinoic acid-metabolizing enzymes, CYP26s, in patterning of CNS. Analysis of mutant mice lacking CYP26s (Cyp26A1, B1, C1) has indicated that CYP26 are expressed in the hindbrain and act as a barrier that protect the anterior portions of the brain from retinoic acid signal.
4. Detection of extra-cellular Nodal and Lefty protein molecules: to detect Nodal and Lefty proteins that have been secreted out from cells, we have generated various transgenic mice that express Nodal and Lefty proteins with a tag (myc, flag, GFP).
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