Morphogenesis and patterning of the vertebrate gut tube.

脊椎动物肠管的形态发生和模式。

• 批准号: 9978856
• 负责人: Nandan L Nerurkar
• 金额: $ 20.25万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-16 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978856
• 关键词: Address; Adult; Anterior; Attention; Automobile Driving; Biomechanics; Biophysics; Cell Therapy; Cells; Chick Embryo; Congenital Abnormality; Congenital Disorders; Data; Detection; Development; Digestion; Electroporation; Embryo; Embryology; Embryonic Structures; Endoderm; Endoderm Cell; Epithelial; Epithelium; Event; Fibroblast Growth Factor; Fluorescent in Situ Hybridization; Foundations; Gastrocoele; Gastrointestinal tract structure; Genes; Goals; Health; Heart; Hindgut; Human; In Situ; Intestines; Knowledge; Light; Limb structure; Malignant Neoplasms; Measurement; Mechanics; Midgut; Molecular; Morphogenesis; Movement; Neural tube; Organ; Pathology; Pattern; Prevalence; Primitive foregut structure; Process; Respiration; Respiratory System; Role; Simple Epithelium; Structure; Testing; Time; Tissues; Tube; Work; base; biophysical analysis; cell motility; experimental study; gastrointestinal; in vivo imaging; insight; mathematical methods; mechanical force; migration; progenitor; regenerative therapy; respiratory; segregation; single molecule; somitogenesis; spatiotemporal; stem cell differentiation; stem cell therapy; stem cells

PROJECT SUMMARY/ABSTRACT The vital functions or respiration and digestion are carried out by organs that arise from an embryonic structure known as the gut tube. Despite its fundamental importance, morphogenesis of the gut tube has been remarkably understudied, particularly when considered alongside concurrent events in the neural tube, heart, limbs, and other tissues of the developing embryo. The purpose of this work is to study how this structure is formed through an integration of biophysical and molecular approaches, with the goal of revealing how progenitor cell movements in the endodermal epithelium are coordinated with differentiation to construct the foregut, midgut, and hindgut through molecular control of mechanical forces. The gut tube, once formed, is a simple epithelial cylinder, yet it arises through spatiotemporally distinct events that separately give rise to the foregut, midgut, and hindgut segments of the tube. These processes are poorly understood, and in particular, how the formation of these three segments are coordinated to form a single continuous tube remains largely unaddressed. Recently, we have turned to the chick embryo to study gut tube morphogenesis, employing live in vivo imaging, electroporation-based gene misexpression, and biomechanical/mathematical approaches to study formation of the hindgut. These studies revealed that much of what was previously assumed from fate mapping studies about gut tube formation may be incomplete, if not incorrect. The present application extends these approaches to study the biophysical role of collective cell movements in foregut morphogenesis, and to elucidate how cells of the presumptive midgut contribute cells to the forming foregut and hindgut. We will perform highly quantitative analyses of cell movements and physical forces in the presumptive foregut and midgut endoderm, and study the emergence of antero-posterior patterning in the context of cell movements along this axis, using single molecule fluorescent in situ detection of established marker genes. Understanding of this critical step in vertebrate development will provide valuable insight into the underlying causes of a broad range of gastrointestinal birth defects. Ultimately, the projects emanating from this work will have important implications for the development of cell-based therapies where directed the differentiation of progenitor cells toward distinct gastrointestinal and respiratory lineages is needed.

项目摘要/摘要 重要功能或呼吸和消化是由胚胎产生的器官进行的 结构称为肠管。尽管具有根本重要性，但肠道的形态发生一直是 大量研究了，尤其是当在神经管中的并发事件旁边考虑时，心脏，心脏， 四肢和发育中的胚胎的其他组织。这项工作的目的是研究这种结构是如何的 通过结合生物物理和分子方法形成，目的是揭示如何 内胚层上皮中的祖细胞运动与分化协调以构建 通过机械力的分子控制，前面，中肠和后肠。 肠管曾经形成，是一个简单的上皮圆柱体，但它通过时空不同而产生 分别引起了管子的前肢，中肠和后肠段的事件。这些过程是 鲜为人知，尤其是这三个部分的形成如何协调以形成A 单个连续管在很大程度上保持不足。最近，我们转向小鸡胚胎学习 肠道的形态发生，采用活体内成像，基于电穿孔的基因和 研究后肠形成的生物力学/数学方法。这些研究表明 以前从命运图的研究中假设的有关肠道形成的研究可能是不完整的，如果不是的话 不正确。本应用扩展了这些方法来研究集体细胞的生物物理作用 前肢形态发生的运动，并阐明假定中肠细胞如何贡献细胞 形成的前身和后肠。我们将对细胞运动和物理的高度定量分析 推定性方面和中肠内胚层中的力，并研究前后孔的出现 使用单分子荧光原位检测，在沿该轴的细胞运动的背景下进行图案 已建立的标记基因。 了解脊椎动物开发中的这一关键步骤将为您提供宝贵的见解 广泛的胃肠道出生缺陷的根本原因。最终，从 这项工作将对基于细胞的疗法的开发具有重要意义 需要将祖细胞分化为不同的胃肠道和呼吸系统谱系。