Patterning and Morphogenesis of the Vertebrate Gut

脊椎动物肠道的模式和形态发生

• 批准号: 7885083
• 负责人: CLIFFORD J. TABIN
• 金额: $ 34.21万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7885083
• 关键词: Affect; Architecture; Attention; Automobile Driving; Biological Models; Cell Adhesion Molecules; Cessation of life; Columnar Epithelium; Congenital Abnormality; Congenital Heart Defects; Cues; Development; Developmental Biology; Dorsal; Elasticity; Embryo; Embryonic Development; Epithelial; Event; Extracellular Matrix; Failure; Feedback; Gastrocoele; Gastrointestinal tract structure; Gene Expression; Genes; Genetic Epistasis; Goals; Growth; Heart; Intestines; Lead; Left; Length; Link; Location; Mediating; Mesenchyme; Mesentery; Midgut; Modeling; Morphogenesis; Morphology; Mus; N-Cadherin; Necrosis; Organ; Organogenesis; Pattern; Phase; Phylogenetic Analysis; Play; Process; Production; Property; Randomized; Regulation; Relative (related person); Repression; Right-On; Role; Rotation; Shapes; Side; Signal Transduction; Specific qualifier value; Staging; Structure; Surface; System; Testing; Three-Dimensional Imaging; Time; Transcriptional Regulation; Tube; Visceral; Work; clinically significant; developmental genetics; notch protein; public health relevance; reconstruction; transcription factor

DESCRIPTION (provided by applicant): The goal of this work is to understand the genetic and developmental underpinnings of organ morphogenesis. In this study, we focus on the problem of looping morphogenesis using the developing midgut as a model system. We previously demonstrated that the chirality of gut rotation (i.e. specification of its rotation in a counterclockwise direction) is mediated by changes in the cellular architecture of the dorsal mesentery. We have identified a number of transcription factors asymmetrically expressed in the dorsal mesentery. In the first Aim we will investigate the role each plays in changing the cellular organization within the mesentery as well as examining their cross regulation to understand the transcriptional network controlling this by first step of gut morphogenesis. In our second Aim we will turn our attention to the later steps of gut morphogenesis. We will examine how each subsequent coiling event relates to the initial decision to coil counter clockwise. We will examine the later roles of specific transcription factors in the process. And we will dissect the roles of physical forces and topological constraints in directing the formation of specific loops during midgut organogenesis. PUBLIC HEALTH RELEVANCE: We are studying looping morphogenesis of the gut. Failure in this process results in serious congenital malformations that, if left uncorrected, can lead to blockage of the GI tract, intestinal necrosis and death. There are also broader implications extending to an understanding of cardiac malformations, as looping morphogenesis is not well understood for any tubal organ, and parallels between the primitive gut tube and its dorsal mesentery with early heart tube and its dorsal mesocardium suggest similar biomechanisms may be involved.

描述（由申请人提供）：这项工作的目标是了解器官形态发生的遗传和发育基础。在本研究中，我们以发育中的中肠为模型系统，重点研究循环形态发生的问题。我们之前已经证明肠旋转的手性（即逆时针方向的旋转）是由背肠系膜细胞结构的变化介导的。我们已经确定了一些转录因子不对称地表达在背肠系膜。在第一个目标中，我们将研究每一个在改变肠系膜内细胞组织中的作用，以及检查它们的交叉调节，以了解肠道形态发生的第一步控制这一转录网络。在我们的第二个目标中，我们将把注意力转向肠道形态发生的后期步骤。我们将研究每个后续的卷取事件如何与逆时针卷取的初始决定相关。我们将研究特定转录因子在这一过程中的作用。我们将剖析物理力和拓扑约束在指导中肠器官发生过程中特定环路形成中的作用。