Analysis of expression and function of regulatory molecules in the whole embryos by new developmetnal engineering system

1.利用体外发育系统，阐明了脑、肾上腺皮质、关节等器官组织发生过程中几种调控分子的功能。将体外系统引入到类似的分析中，设计并部分启动了以下分子的分析。(Otani)2.K-ras(-/-)小鼠胚胎致死，胚胎心脏极薄，而H-ras(-/-)和N-ras(-/-)小鼠在其一生中表现正常。H-ras(-/-)N-ras(-/-)和H-ras(/-)N-ras(/-)K-ras(/-)小鼠是存活的，提示K-ras基因的双等位表达或N-ras和K-ras基因的单等位表达对小鼠的发育是足够的。(AIBA)3.我们克隆了人死亡相关蛋白激酶(DAP Kinase)的大鼠同源基因。在胚胎15天，DAP激酶在整个神经轴的外套膜区和脑室区均有表达。出生后，该基因在大脑中的表达显著下降，但在几个重组…中保持不变更多的成熟神经元群体，这表明DAP激酶部分参与了程序性神经元的死亡，但也参与了包括突触可塑性在内的其他神经元功能。(Sakagami)4.我们确定了几个候选的Hox基因靶点，包括线虫基因mab21(Mmb)的小鼠同源物。为了分析MMAb的功能，我们建立了转基因小鼠，并制备了针对MMAb基因产物的抗体。(Takahashi)5.我们鉴定并鉴定了新的果蝇蛋白激酶Dnrk和Dmnk，它们分别在发育中的神经系统和建立过程中的生殖系中特异表达。我们还鉴定了Dnrk、mRor1和mRor2的小鼠同源基因。我们现在正在研究它们在神经系统发育中的功能作用。(Minami)6.我们发现同源异型盒基因Goosecid突变小鼠在气管、附件骨骼和外生殖器中显示出异常。根据Goosecid和Msx1基因相似的表达模式和敲除表型，为它们创造了双KO小鼠。这些数据表明，在中耳骨的图案化过程中存在一些基因交互作用。(山田)更少

1. Using exo utero development system, functions of several regulatory molecules in the histogenesis of the organs including brain, adrenal cortex, and joints were elucidated. Introduction of exo utero system to the similar analyzes on the following molecules were designed and have been partially initiated. (Otani)2. K-ras (-/-) mice are embryonic lethal and the embryonic heart has extremely thin wall, whereas H-ras (-/-) and N-ras (-/-) mice appear normal throughout their life span. H-ras (-/-) N-ras (-/-), and H-ras (+/-) N-ras (+/-) K-ras (+/-) mice are viable, suggesting that biallelic expression of K-ras gene or monoallelic expression of both N-ras and K-ras genes are sufficient for mouse development. (Aiba)3. We cloned a rat homologue of the human Death-associated protein kinase (DAP kinase). DAP kinase was expressed in both mantle and ventricular zones of the entire neuraxis on E15. The expression decreased markedly after birth in the brain, but was maintained in several restric … More ted mature neuronal populations, suggesting that DAP kinase is involved partially in the programd neuronal cell death but in other neuronal functions including synaptic plasticity. (Sakagami)4. We identified several candidate Hox gene targets, including a mouse homologue of the C.elegans gene mab21 (mmb). To analyze the function of mmab we generated transgenic mice and prepared antibodies against mmab gene product. (Takahashi)5. We have identified and characterized novel Drosophila protein kinases, Dnrk and Dmnk, expressed specifically in the developing nervous system and in germline during its establishment, respectively. We have also identified and characterized mouse orthologs of Dnrk, mRor1 and mRor2. We are now investigating their functional roles in the development of the nervous system. (Minami)6. We showed that homeobox gene Goosecoid mutant mice display abnormalities in the trachea, appendicular skeleton and external genitalia. Given the similar expression pattern and the knock-out phenotypes of the Goosecoid and Msx1 genes, the double ko mice for them were created. The data imply the presence of some genetic interactions involved in the patterning of middle ear bones. (Yamada) Less