Functional dissection of drosophila homeodomain transcription factors required for development of the body plan

几乎所有的动物沿着前后（头到尾）轴都表现出某种形式的分割。 人体计划的分割的示例是脊柱的椎骨;每个椎骨表示单独的节段，并且每个椎骨具有唯一的形状或形态。 我对两个一般性问题感兴趣：第一，如何建立正确的片段数量;第二，如何为片段分配唯一的形态。 昆虫体平面沿前后轴沿着分为14个节段单元。 果蝇fushi tarazu基因编码确定发育过程中形成的片段的正确数量所需的FTZ蛋白，而长鼻足（pb）和性梳减少（Scr）基因编码将独特身份分配给3个片段所需的蛋白PB和SCR。 FTZ、SCR和PB共享称为同源结构域（HD）的DNA结合蛋白结构域。 含HD蛋白是调节转录的转录因子，转录是将存储在DNA中的信息转化为RNA的过程，然后由蛋白质合成机制读取。 尽管许多受FTZ、PB和SCR调控的基因被广泛表征，但缺乏关于这些转录因子如何工作以改变基因转录模式的知识。 HD转录因子已经被分析了二十多年，但了解它们如何工作的一个关键因素是对其功能结构域的完整描述。 绘制功能域已被证明是困难的。 这种困难是由于含HD的蛋白质由小肽基序组成，这些小肽基序对整体活性的贡献很小。 我们现在正在识别这些小图案并描述它们的要求。 这些知识将大大提高我们对昆虫体平面分割背后的机械逻辑的理解，并且由于在脊椎动物体平面分割期间也需要含HD的蛋白质，因此在苍蝇中的工作具有普遍的生物学意义和应用。

Nearly all animals exhibit some form of segmentation along the anterior-posterior (head to tail) axis. An example of segmentation of the human body plan is the vertebrae of the backbone; each vertebra represents an individual segment and each vertebra has a unique shape or morphology. I am interested in two general questions: first how the correct number of segments is established; and second how segments are assigned a unique morphology. The insect body plan is divided into 14 segmental units along the anterior-posterior axis. The fruitfly fushi tarazu gene encodes the FTZ protein required for determining the correct number of segments that form during development, and the proboscipedia (pb) and Sex combs reduced (Scr) genes encode proteins PB and SCR required for assigning unique identities to 3 segments. FTZ, SCR and PB share a DNA-binding protein domain called the homeodomain (HD). HD-containing proteins are transcription factors that regulate transcription, which is the process that converts information stored in DNA to RNA that is then read by the protein synthesis machinery. Though many of the genes regulated by FTZ, PB and SCR are extensively characterized, there is a lack of knowledge about how these transcription factors work to bring about changes in the pattern of gene transcription. HD-transcription factors have been analyzed for over twenty years, but one key element missing to understand how they work is a complete description of their functional domains. Mapping the functional domains has proven difficult. This difficulty is due to HD-containing proteins being composed of small peptide motifs that make only small contributions to overall activity. We are now identifying these small motifs and describing their requirements. This knowledge will greatly enhance our understanding of the mechanistic logic behind the segmentation of the insect body plan, and as HD-containing proteins are also required during the segmentation of the vertebrate body plan, the work in flies is of general biological significance and application.