Mechanism of head formation

在这个项目中，我们研究了未来头部如何在小鼠胚胎中被指定、诱导和形成。特别关注了以下四个主题。前后极性是如何确定的：我们已经研究了DVE（远端内脏内胚层）是如何在原肠胚前形成的，并揭示了BMP信号在DVE形成中的作用。节点信号在头形成中的作用：节点信号在头形成中起重要作用，它是由转录因子FoxH1介导的。为了了解Nodal头部形成的机制，我们系统地搜索了小鼠基因组中FoxH1调控的基因，并确定了大约150个候选基因。我们现在正在检查它们在野生型和FoxH1突变胚胎中的表达模式。至少，一些基因是真正的foxh1靶标，因为它们在突变胚胎中的表达受损。视黄酸对中枢神经系统的区域化：我们研究了视黄酸代谢酶cyp26在中枢神经系统模式中的作用。对缺乏CYP26s （Cyp26A1, B1, C1）的突变小鼠的分析表明，CYP26在后脑表达，并作为一个屏障，保护大脑前部免受视黄酸信号的影响。细胞外Nodal和Lefty蛋白分子的检测：为了检测细胞外分泌的Nodal和Lefty蛋白，我们培育了各种转基因小鼠，这些小鼠表达带有标记（myc, flag， GFP）的Nodal和Lefty蛋白。

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).