RNA dynamics in the developing mouse face

小鼠面部发育中的 RNA 动态

• 批准号: 8725550
• 负责人: JOAN E HOOPER
• 金额: $ 28.3万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-03 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725550
• 关键词: Accounting; Affect; Alternative Splicing; Animal Model; Automobile Driving; Behavior; Bioinformatics; Biological Models; Biology; Cells; Child; Chromatin; Competence; Complement; Complex; Computers; Congenital Abnormality; Data Set; Databases; Defect; Development; Dysmorphology; Ectoderm; Ectoderm Cell; Endoderm; Enhancers; Epithelial; Erinaceidae; Event; Face; Fibroblast Growth Factor; Fibroblast Growth Factor Receptor 2; Future; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Gene Expression Regulation; Genes; Genetic; Genetic Predisposition to Disease; Genetic Transcription; Genomics; Head; Health; Human; Infant; Knockout Mice; Knowledge; Ligands; Mediating; Mesenchymal; Mesenchyme; Messenger RNA; MicroRNAs; Minor; Modeling; Molecular Genetics; Mono-S; Morphogenesis; Morphology; Movement; Mus; Neural Crest; Parents; Pathway interactions; Pattern; Phenotype; Population; Process; Quality of life; RNA; RNA Polymerase II; RNA Splicing; Reagent; Regulation; Resources; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Skeleton; Staging; Systems Biology; Tissue Sample; Tissue-Specific Gene Expression; Tissues; Transgenic Mice; Translations; craniofacial; cranium; critical period; malformation; mouse model; oral tissue; orofacial; prevent; promoter; recombinase; signal processing; transmission process

Craniofacial morphogenesis is a complex process requiring coordinated proliferation, movement and differentiation of six distinct facial prominences. The complexity of this process leaves it vulnerable to environmental and genetic perturbations, such that craniofacial malformations are one of the most common classes of birth defects. Facial prominences are made up of a mono-layer of ectoderm encasing a large core of neural crest- and mesodermally-derived mesenchymal cells. Signaling from this minor population of ectodermal cells directs and coordinates the behavior of the underlying mesenchyme, and thence facial morphogenesis. Manipulations that alter these signaling processes and tissue interactions have grave consequences for facial development, resulting in various types of medically important dysmorphology including orofacial clefting. Thus a detailed knowledge of geno-dynamics of the ectoderm is an essential component of the overall description of facial development. In this proposal a multi-disciplinary team has been assembled with expertise in craniofacial biology, mouse molecular genetics, bioinformatics and computer biology to gain a Systems Biology level understanding of early mammalian facial development. The ectoderm and the mesenchyme of the wild-type facial prominences will be separated at critical timepoints encompassing facial morphogenesis, then these separated tissues will be used to generate contrasting dynamic spatio-temporal profiles of gene expression and post-translational RNA regulation at the level of splicing, turnover, and translation. These combined studies should provide a valuable resource detailing the dynamic interplay of ectoderm and mesenchyme during normal facial development.

颅面形态发生是一个复杂的过程，需要六个不同面部突起的协调增殖、运动和分化。这一过程的复杂性使其容易受到环境和遗传扰动的影响，因此颅面部畸形是最常见的出生缺陷之一。面部突起由单层外胚层组成，外胚层包裹着大量神经嵴和中胚层衍生的间充质细胞核心。来自这一少数外胚层细胞的信号引导和协调底层间充质的行为，从而指导和协调面部形态发生。改变这些信号过程和组织相互作用的操作会对面部发育产生严重后果，导致各种类型的医学上重要的畸形，包括口面部裂。因此，外胚层基因动力学的详细知识是面部发育整体描述的重要组成部分。在该提案中，组建了一个具有颅面生物学、小鼠分子遗传学、生物信息学和计算机生物学专业知识的多学科团队，以获得对早期哺乳动物面部发育的系统生物学水平的了解。 野生型面部突起的外胚层和间充质将在面部形态发生的关键时间点分离，然后这些分离的组织将用于在剪接、周转和翻译水平上产生基因表达和翻译后RNA调控的对比动态时空特征。这些综合研究应该提供宝贵的资源，详细说明正常面部发育过程中外胚层和间质的动态相互作用。