MOLECULAR BIOLOGY OF HYDRA DEVELOPMENT

蛋白酪氨酸激酶受体是一种重要的细胞因子。 多细胞动物的发育信号。该项目的目标是 在这方面的应用是了解受体蛋白-酪氨酸是如何 在简单的动物九头蛇的发育过程中使用了激酶。 对于这些研究来说，九头蛇作为一个系统的吸引力在于 其结构组织和发展的简单性。首字母 将采取的方法将包括完成分子 九头蛇属的一个基因的特征 发育重要的一类受体蛋白-酪氨酸激酶 脊椎动物。该受体的克隆基因将为 确定息肉中哪些细胞产生受体。用方法 它是我们为引入克隆基因和合成 将寡核苷酸注入水电，将有可能进行增益 功能和丧失功能的实验，以确定哪些发育 过程取决于我们分离出的基因所在的受体。通过 表达研究可能会发现，该受体在 干细胞或特定发育谱系的特定前体细胞。 如果是这样的话，我们可以使用针对受体的抗体来分离细胞 它表达了这一点。这些分离的细胞可以被引入干细胞- 耗尽的九头蛇息肉以确定它们的发育命运。是这样的 信息将有助于理解通过该受体的输入如何 指导细胞的发育。因为受体蛋白-酪氨酸 在动物进化过程中，激酶被保存得如此之好，决定了 他们在九头蛇开发中的作用应该让我们深入了解这些 蛋白质在更复杂的动物的发育过程中发挥作用。这口井- 细胞中受体蛋白-酪氨酸激酶的研究进展 生长分化及其转化为致癌的能力 形态表明，对这些蛋白质所扮演的角色的理解 将对理解、诊断和治疗人类 从癌症到出生缺陷的各种疾病。

Protein-tyrosine kinase receptors are important mediators of developmental signals in multicellular animals. The goal of the project in this application is to understand how receptor protein-tyrosine kinases are used in developmental processes in the simple animal Hydra. The attraction of Hydra as a system for these studies lies in the extreme simplicity of its structural organization and development. The initial approach to be taken will involve completing the molecular characterization of a gene from Hydra which is a member of a developmentally important class of receptor protein-tyrosine kinases in vertebrates. The cloned gene for this receptor will provide reagents for determining what cells in the polyp produce the receptor. With methods which we have developed for introduction of cloned genes and synthetic oligonucleotides into Hydro, it will be possible to carry out gain of function and loss of function experiments to determine what developmental processes depend on the receptor whose gene we have isolated. By expression studies it may be found that the receptor is expressed in the stem cells or committed precursors of a particular developmental lineage. If so, we can use antibodies against the receptor to isolate the cells which express it. These isolated cells can be introduced into stem cell- depleted Hydra polyps to determine their developmental fates. Such information will help in understanding how input via this receptor directs the development of cells. Because receptor protein-tyrosine kinases have been so well conserved during animal evolution, determining their roles in Hydra development should provide insight into how these proteins function in development in more complex animals. The well- documented involvement of receptor protein-tyrosine kinases in cell growth and differentiation and their ability to be converted to oncogenic forms indicate that an understanding of the roles these proteins play will have implications for understanding, diagnosing, and treating human diseases ranging from cancer to birth defects.