Roles of homeobox genes in neural development and behavior

BarH1和BarH2是两个密切相关的同源框基因，它们在果蝇X染色体的Bar基因座上形成一个小复合体。这些基因编码的多肽在大小和序列上相似，并共享一个共同的同源结构域，除了假定的反式激活物结合位点外，该结构域在序列上是相同的。它们在各种类型的神经细胞中严格共表达，在功能上相互冗余，是某些神经组织发育所必需的。作为阐明Bar Homeobox基因严格共表达的第一步，我们从分子水平上解剖了BarH1和BarH2之间约80kb的区域，并利用P介导的转化和lac-Z报告系统在个体水平上分析了它们的增强子活性。我们鉴定并定位了该区域几乎所有的Bar特异性增强子(15个启动子)，这一观察结果支持BarH1和BarH2基因受一系列共同的增强子元件调控的观点。在实验过程中，我们还分离了相关基因并检测了它们的性质。它们包括两个成纤维细胞生长因子受体基因，刺猬片段极性基因，分叉基因，鹰神经母细胞特异性激素受体基因和NAD(P)H-黄素氧化还原酶基因。此外，我们还研究了Bar同源框基因与Hedgehog之间可能的相互作用，发现在特定情况下，Bar Homeobox基因的时空表达严格受Hhegehog和另一个关键片段极性基因wingless形成的位置信息的控制。

BarH1 and BarH2 are two closely related homeo box genes that form a small complex at the Bar locus on the X chromosome of Drosophila. These genes encode polypeptides similar in size and sequence and share a common homeodomain that is identical in sequence except for the putative trans-activator-binding sites. They are strictly coexpressed in various types of neural cells, functionally redundant to each other, and are required for development for some neural tissues. As a first step to clarify how the strict coexpression of Bar homeobox genes are regulated, about 80kb region spanning between BarH1 and BarH2 were molecularly dissected and their enhancer activity was assayd at the level of individuals using P-mediated transformation and a lac-Z reporter system. We identified and localized almost all Bar-specific enhancers (15 enhnacers) in the region, an observation supporting the notion that BarH1 and BarH2 genes are regulated by a series of common enhancer elements. During the course of experiments, we also isolated related genes and examined their propertiss. They include two FGF receptor genes, hedgehog segment polarity gene, forked gene, eagle neuroblast-specific hormon receptor gene and NAD (P) H-flavin oxidoreductase genes. In addition, we examined possible interactions between Bar homeobox genes and hedgehog, and foundthat, in a particular case, the spatial and temporal expression of Bar homeobox genes are strictly controlled by the positional information formed by hesgehog and wingless, another key segment polarity gene.