Specificity in Homeotic Response Elements

同源异型反应元件的特异性

• 批准号: 8507243
• 负责人: WILLIAM JAMES MCGINNIS
• 金额: $ 27.39万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-09 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507243
• 关键词: Amaze; Animals; Anterior; Arthropods; Bilateral; Brain; Brain region; Cell Nucleus; Cells; Chordata; Communication; Congenital Abnormality; DNA; Data; Development; Distal; Drosophila genus; Educational process of instructing; Embryo; Enhancers; Evolution; Family; Genes; Genetic; Genetic Transcription; Head; Hemothorax; Homeobox; Homeobox Genes; In Situ Hybridization; Individual; Instruction; Knowledge; Mammals; MicroRNAs; Modeling; Neuroectoderm; Pattern; Principal Investigator; Regulator Genes; Research; Resolution; Response Elements; Specificity; Testing; Transcriptional Activation; Vertebrates; appendage; base; fascinate; innovation; promoter; transcription factor

Homeobox genes are an ancient family of developmental regulators that pattern animal embryos. We are fascinated by the genetic circuitry involving homeobox genes that assigns developmental fates to different cells in embryos, and how the redeployment of such circuits has helped to evolve morphological diversity during animal evolution. One aim is to test the idea that a function of microRNAs is to dampen the deleterious effects of sporadic transcription of developmental regulatory genes, such as those of the homeobox family. Another aim is based on our finding that genes of the core proximodistal appendage- patterning network of arthropods are expressed in the anterior neuroectoderm of Drosophila embryos, as well as in the anterior neuroectoderm of chordate embryos in an overlapping anteroposterior order. These genes encode the transcription factors Distal-less, apterous, dachshund, hemothorax, and buttonhead/Sp8. These results, in concert with existing expression data from a variety of other animals, including mammals, suggest that a pre-existing gene network for anterior head patterning, which eventually results in different regional specializations of the brain, was co-opted to pattern the proximodistal axis of bilateral appendages in animals. This model needs more experimental tests, and such tests are outlined in this proposal. These include testing for conserved cross-regulatory relationships among these genes in the anterior neuroectoderm of Drosophila embryos, and testing whether the same set of genes are expressed in the heads of animals that represent the common ancestors of present day arthropods and vertebrates. If validated, this model would represent an amazing example of how a gene network has been redeployed to innovate new morphological features in animal body plans. Another aim is to use high resolution in situ hybridization to study how certain homeobox genes are transcriptionally activated by long-range DNA enhancers at the level of individual genes in individual embryonic nuclei. RELEVANCE (See Instructions): This research will teach us more about how environmental influences alter activities of developmental control genes, which may underlie sporadic birth defects. This research will also increase our knowledge of the genetic circuitry that controls which cells in the developing head of embryos become different regions of the brain.

同源基因基因是一个古老的发育调节剂家族，它们是模样动物胚胎的。我们是 被涉及同源物基因的遗传回路着迷，该基因将发展命运分配给不同 胚胎中的细胞，以及此类电路的重新部署如何有助于发展形态多样性 在动物进化过程中。一个目的是测试microRNA的功能是抑制 发育调节基因的零星转录的有害影响，例如 Homeobox家族。另一个目的是基于我们的发现，即核心近端附属物的基因 - 节肢动物的图案网络在果蝇胚胎的前神经外胚层中表达，如 以及在重叠的前后序列中的脊柱胚胎的前神经外胚层中。这些 基因编码转录因子远端，无焦点，腊肠犬，血胸和纽扣/sp8。 这些结果与来自其他各种动物（包括哺乳动物）的现有表达数据一致 提示用于前头模式的预先存在的基因网络，最终导致不同 大脑的区域专业人士被选中以模拟双侧附属物的近端轴 在动物中。该模型需要更多的实验测试，并且在此提案中概述了此类测试。这些 包括对这些基因之间保守的交叉调节关系的测试 果蝇胚胎的神经外胚层，并测试是否在 代表当今节肢动物和脊椎动物的共同祖先的动物头。如果 经过验证，该模型将代表一个令人惊奇的例子，说明了如何重新部署基因网络 创新动物身体计划中的新形态特征。另一个目的是使用高分辨率原位 杂交研究如何通过远距离DNA转录激活某些同源基因 单个胚胎核中单个基因水平的增强子。 相关性（请参阅说明）： 这项研究将教会我们更多有关环境如何影响发展控制活动的活动 基因，这可能是零星出生缺陷的基础。这项研究还将增加我们对 控制胚胎发育中哪些细胞的遗传回路变成了不同的区域 脑。