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

几乎所有的动物都表现出沿前后(头到尾)轴的某种形式的节段。人体平面分割的一个例子是脊椎骨；每个椎骨代表一个单独的节段，每个椎骨都有独特的形状或形态。我对两个一般性问题感兴趣：第一，如何确定正确的分段数量；第二，如何为分段分配唯一的形态。昆虫体平面沿前后轴线分为14个节段单元。果蝇Fushi Tarazu基因编码FTZ蛋白，确定发育过程中形成的正确片段数量所需的蛋白质；鼻子足虫(PB)和性梳减少(SCR)基因编码蛋白质PB和SCR，为3个片段分配唯一身份。FTZ、SCR和PB共享一个DNA结合蛋白结构域，称为同源域(HD)。含HD的蛋白质是调节转录的转录因子，转录是将储存在DNA中的信息转换为RNA，然后由蛋白质合成机器读取的过程。虽然许多受FTZ、PB和SCR调控的基因都有广泛的特征，但对于这些转录因子如何作用于基因转录模式的改变缺乏了解。HD转录因子已经被分析了20多年，但要了解它们是如何工作的，一个关键因素是对它们的功能结构域的完整描述。绘制功能域已被证明是困难的。这一困难是由于含有HD的蛋白质由小肽基序组成，这些小肽基序对整体活性只有很小的贡献。我们现在正在识别这些小主题并描述它们的需求。这些知识将极大地提高我们对昆虫身体平面分割背后的机制逻辑的理解，由于脊椎动物身体平面分割过程中也需要含有HD的蛋白质，因此在苍蝇身上的工作具有普遍的生物学意义和应用价值。

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.