The systems developmental biology of zebrafish body elongation

斑马鱼身体伸长的系统发育生物学

• 批准号: 10806332
• 负责人: SCOTT A HOLLEY
• 金额: $ 3.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10806332
• 关键词: Biological; Biomechanics; Biophysics; Cell Adhesion Molecules; Cells; Cellular Morphology; Computer Models; Congenital Abnormality; Data Analyses; Development; Developmental Biology; Embryo; Embryology; Embryonic Development; Genetic; Human Development; Image; Mechanics; Methods; Modeling; Molecular; Morphogenesis; Pattern; Pattern Formation; Protein Dynamics; Reproducibility; Research; Role; Spinal Dysraphism; System; Tissues; Vertebral column; Zebrafish; cell behavior; follow-up; in vivo; insight; programs; scoliosis; single molecule

This research program focuses on the systems developmental biology, biophysics and biomechanics of early spinal column development. The research program utilizes zebrafish as model for understanding the mechanisms of human development and causes of birth defects such as scoliosis and spina bifida. The experimental approach is driven by the idea that quantitative in vivo analysis will lead to fundamental insights into the emergence of biological organization from the collective interaction of its constituent parts. The research program combines genetics, embryology, in vivo biophysics, live imaging and systems level data analysis and computational modeling to study pattern formation and morphogenesis. The proposed research program will address a number of questions regarding biological order and the reproducibility of embryonic development. The program will follow-up on the lab’s recent finding that a dynamically stable pattern of cell state transitions underlies the reproducibility of development to understand the mechanisms maintaining dynamic stability during zebrafish body elongation. The research program will also examine the mechanism of mechanical information regulating the flux of cells through a developmental trajectory. The program will address how tissue-tissue interactions constrain cell behavior during body elongation. At the molecular and cellular level, the program will utilize newly developed methods for in vivo single molecule biophysics to study cell adhesion protein dynamics and their relation to cell state transitions and cell morphology. Overall, this is multi-scale research program that considers the roles of molecules, cells and tissues in the genesis of order in the developing embryo.

这项研究的重点是系统发育生物学、生物物理学和 脊柱早期发育的生物力学。该研究项目利用斑马鱼作为 理解人类发育机制和出生缺陷原因的模型 如脊柱侧弯和脊柱裂。实验方法是由这样一种想法驱动的 体内的定量分析将导致对生物学的出现的基本洞察 组织来自其组成部分的集体互动。研究计划 结合遗传学、胚胎学、活体生物物理学、实时成像和系统级数据分析 以及用于研究图案形成和形态发生的计算建模。建议数 研究计划将解决一些关于生物秩序和 胚胎发育的再生性。该项目将跟进实验室最近的发现 细胞状态转变的动态稳定模式是可重复性的基础 斑马鱼体内维持动态稳定性机制的研究进展 伸长率。该研究计划还将研究机械信息的机制 通过发育轨迹调节细胞的流量。该计划将解决如何 在身体伸长过程中，组织与组织之间的相互作用限制了细胞的行为。在分子和 在细胞层面，该计划将利用新开发的方法在体内进行单分子研究 生物物理学研究细胞黏附蛋白动力学及其与细胞状态转变和 细胞形态。总体而言，这是一个多尺度的研究计划，它考虑了 分子、细胞和组织在发育中胚胎有序的发生中。