Growth and patterning in the gut mesenchyme

肠道间质的生长和模式

• 批准号: 9247172
• 负责人: Junhao Mao
• 金额: $ 36.18万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9247172
• 关键词: Address; Applications Grants; Cell Culture Techniques; Complex; Development; Differentiation and Growth; Disease; Embryo; Embryonic Development; Endoderm; Epithelial; Epithelium; Erinaceidae; FRAP1 gene; Fibroblasts; Gastrointestinal Diseases; Gastrointestinal tract structure; Genetic; Genetic Transcription; Genetic study; Germ-Line Mutation; Grant; Growth; Homeostasis; Hyperplasia; Intestinal Polyposis; Intestines; Knowledge; Maintenance; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Mediating; Mediator of activation protein; Mesenchymal; Mesenchymal Differentiation; Mesenchyme; Mesoderm Cell; Molecular; Mus; Muscle; NUAK1 gene; Organ Size; Organogenesis; Pathway interactions; Patients; Pattern; Peutz-Jeghers Syndrome; Phenotype; Phosphotransferases; Play; Polyps; Proteins; Role; SOX11 gene; SOX4 gene; STK11 gene; Serum Response Factor; Signal Pathway; Signal Transduction; Smooth Muscle; Smooth Muscle Myocytes; System; Testing; Tissues; Transcriptional Regulation; Up-Regulation; cell type; design; differential expression; gastrointestinal; genetic manipulation; in vivo; insight; myocardin; novel; novel therapeutic intervention; novel therapeutics; polyposis; postnatal; progenitor; protein function; public health relevance; smoothened signaling pathway; transcription factor

DESCRIPTION (provided by applicant): Organogenesis and tissue homeostasis within the gastrointestinal (GI) tract require continuous crosstalk between the endodermal epithelium and adjacent mesenchyme. Much of what is known about GI development has been learned from studies of the endoderm and its derivatives; however, little is known about the genetic and cellular mechanisms governing gut mesenchymal development. This grant application is designed to uncover the mechanisms that underlie this important, yet poorly understood developmental system. The proposed studies are centered on charactering on the molecular basis of growth and patterning in the gut mesenchyme. We will use a combination of mouse genetics and cellular approaches to address three principle questions. First, we will define a Sox-dependent molecular switch that is responsible for coordinating early primitive progenitor expansion and subsequent mesenchymal differentiation. In the second part of the grant, we will identify the signaling pathways that act in concert to control smooth muscle growth and intestinal organ size. In the third part of the grant, we will explore a novel mesenchymal mechanism that is involved in suppression of intestinal polyposis. We believe that completion of the proposed studies will significantly further our understanding of the fundamental mechanisms controlling gut development and homeostasis. This knowledge gained from our studies will ultimately contribute to the development of new therapies for treating GI-related diseases and cancers.

描述（由申请人提供）：胃肠（GI）道内的器官发生和组织稳态需要内胚层上皮和相邻间充质之间的连续串扰。许多关于GI发育的知识都是从内胚层及其衍生物的研究中了解到的;然而，对控制肠道间充质发育的遗传和细胞机制知之甚少。这项资助申请旨在揭示这一重要但知之甚少的发育系统的机制。拟议的研究集中在肠间充质中的生长和模式化的分子基础上表征。我们将使用小鼠遗传学和细胞方法的组合来解决三个主要问题。首先，我们将定义一个Sox依赖的分子开关，负责协调早期原始祖细胞扩增和随后的间充质分化。在资助的第二部分，我们将确定共同控制平滑肌生长和肠道器官大小的信号通路。在第三部分的补助金，我们将探索一种新的间充质机制，参与抑制肠息肉病。我们相信，完成拟议的研究将显着进一步我们的基本机制控制肠道发育和稳态的理解。从我们的研究中获得的这些知识最终将有助于开发治疗GI相关疾病和癌症的新疗法。