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.

该研究计划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。该研究计划利用斑马鱼作为 了解人类发育机制和出生缺陷原因的模型 例如脊柱侧凸和脊柱裂。实验方法是由这样一个想法驱动的， 定量体内分析将导致对生物学的出现的基本见解， 组织是由其组成部分的集体相互作用产生的。研究计划 结合了遗传学、胚胎学、体内生物物理学、实时成像和系统级数据分析 和计算建模来研究图案形成和形态发生。拟议 研究计划将解决一些关于生物秩序的问题， 胚胎发育的可重复性。该项目将跟进实验室最近的发现， 细胞状态转换的动态稳定模式是 发展，以了解机制，维持动态稳定性，在斑马鱼的身体 伸长率该研究计划还将研究机械信息的机制 通过发育轨迹来调节细胞的流动。该计划将解决如何 组织-组织相互作用在身体伸长期间约束细胞行为。在分子和 细胞水平，该计划将利用新开发的方法，在体内单分子 生物物理学研究细胞粘附蛋白动力学及其与细胞状态转换的关系， 细胞形态学总的来说，这是一个多尺度的研究项目，考虑了 分子、细胞和组织在胚胎发育过程中的作用。