HOMEOBOX GENE REGULATION IN C ELEGANS DEVELOPMENT

在线虫线虫中，九种感官的特定身份 雄性尾部的射线是由同源异型簇组合控制的 (Hom-C)基因。这项建议的长期目标是理解 生成此Hom-C表达式模式的方法， 特别强调一个关键成分，HOX基因EGL-5。 由于脊椎动物的发育采用了类似的策略，这项研究 将对理解人类发展和发展具有相关性 缺陷。这里提出了一种双重实验方法。首先，一个 将进行基因筛查以隔离有缺陷的动物 EGL-5的表达模式。这种方法是可行的，因为 EGL-5表达的错误调节被预测会导致特定的， 雄性尾巴结构中可识别的突变表型。这 可能允许识别和表征作用于 生成Hom-C表达模式。同时，一种分子方法 将采取：使用报告基因构建，调节元件 对野生型是必要和充分的EGL-5基因 表情模式将被描绘出来。这些元素所使用的手段 然后将对功能进行研究；在突变筛选中确定的基因可能 成为通过这些要素发挥作用的候选监管因素。这 这项工作应该揭示Hom-C基因密码的产生，它 仍然是发育生物学中一个重要而有趣的问题。

In the nematode C. elegans, the specific identities of the nine sensory rays in the male tail are combinatorially controlled by homeotic-cluster (HOM-C) genes. The long-term goal of this proposal is to understand the means by which this HOM-C expression pattern is generated, with particular emphasis on one critical component, the Hox gene egl-5. Because vertebrate development employs similar strategies, this research will have relevance for understanding human development and developmental defects. A two-fold experimental approach is proposed here. First, a genetic screen will be performed to isolate animals which have defective egl-5 expression patterns. This approach is feasible because misregulation of egl-5 expression is predicted to cause specific, identifiable mutant phenotypes in the structure of the male tail. This may allow the identification and characterization of genes which act to generate HOM-C expression patterns. Concurrently, a molecular approach will be taken: using a reporter gene construct, the regulatory elements of the egl-5 gene which are necessary and sufficient for its wild-type expression pattern will be delineated. The means by which these elements function will then be studied; genes identified in the mutant screen may be candidate regulatory factors which act through these elements. This work should shed light on the generation of HOM-C gene codes, which remains an important and interesting problem in developmental biology.