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，阐明了几种调节分子在脑、肾上腺皮质和关节等器官组织发生中的功能。设计并部分启动了体外系统对以下分子的类似分析。(大谷)2。K-ras（-/-）小鼠具有胚胎致死性，胚胎心脏壁极薄，而H-ras（-/-）和N-ras（-/-）小鼠在其整个生命周期中表现正常。H-ras (-/-) N-ras（-/-）和H-ras (+/-) N-ras (+/-) K-ras（+/-）小鼠均能存活，表明K-ras基因双等位基因表达或N-ras和K-ras基因单等位基因表达足以促进小鼠发育。(Aiba) 3。我们克隆了一个人类死亡相关蛋白激酶（DAP激酶）的大鼠同源物。在E15上，整个神经轴的套膜区和心室区均有DAP激酶的表达。出生后，DAP激酶在大脑中的表达明显下降，但在一些受限的成熟神经元群体中却保持不变，这表明DAP激酶部分参与程序性神经元细胞死亡，但也参与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Hox基因靶点，包括秀丽隐杆线虫基因mab21 （mmb）的小鼠同源物。为了分析mmab基因的功能，我们建立了转基因小鼠并制备了抗mmab基因产物的抗体。(高桥)5。我们已经鉴定并鉴定了新的果蝇蛋白激酶，Dnrk和Dmnk，分别在发育中的神经系统和生殖系中特异性表达。我们还鉴定并鉴定了小鼠Dnrk、mRor1和mRor2的同源基因。我们现在正在研究它们在神经系统发育中的功能作用。(南城)6。我们发现同源盒基因鹅样突变小鼠在气管、附属骨和外生殖器中表现出异常。考虑到Goosecoid和Msx1基因相似的表达模式和敲除表型，我们建立了它们的双ko小鼠。这些数据暗示了在中耳骨的形成过程中存在一些基因的相互作用。(Yamada)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