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Mechanics of Vertebrate Embryo Elongation

脊椎动物胚胎伸长的力学

基本信息

批准号：
9912796
负责人：
OLIVIER POURQUIE
金额：
$ 54.66万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-20 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9912796
关键词：
4D Imaging Automobile Driving Behavior Biological Biomechanics Birds Body part Cancer Biology Cells Chickens Computer Models Congenital Abnormality Data Defect Development Developmental Biology Diffusion Elements Embryo Embryonic Development Exposure to Fibroblast Growth Factor Gases Generations Goals Growth Image Injections Knowledge Lead Light Limb structure Logic Measures Mechanics Mesoderm Mesoderm Cell Modeling Molecular Movement Musculoskeletal Neural tube Paraxial Mesoderm Physics Process Production Property Quail Regenerative Medicine Resistance Rheology Role Sacral agenesis Signal Transduction Spinal Dysraphism Structure Tail Techniques Temperature Testing Time Tissues Transgenic Organisms Work base biophysical techniques cell motility experimental study in vivo particle exposure physical model pressure progenitor stem cells time use vertebrate embryos

项目摘要

Project Summary/Abstract The posterior part of the body is progressively formed from a structure called tail bud (TB). Defects in this process lead to severe birth defects such as spina bifida or caudal agenesis. The progressive elongation of the posterior body requires the generation of forces controlling TB regression and a constant supply of progenitors to generate the forming tissues. In previous work, we have shown that in the chicken embryo the process driving body elongation from the TB involves the posterior presomitic mesoderm (PSM) where cells establish a gradient of random cell motility (cell diffusion) downstream of FGF signaling (Benazeraf et al, 2010). Together with our co-PI Mahadevan, we have elaborated a new physical framework proposing that the gradient of cell diffusion acts to generate forces involved in the elongation movements much like gas particles exposed to a gradient of temperature generate pressure (Regev et al, 2017). Our models are based on a minimal number of parameters: cell diffusion gradient, rate of cell addition to the PSM, and tissue mechanical resistance, leading to a unidirectional elongation force. Here, we will measure these parameters in vivo by combining developmental biology, imaging and soft matter physics approaches with the goal of predicting the rate of embryo elongation as a function of space and time. We first propose to study the cellular basis of the cell diffusion gradient and the role of FGF signaling in its formation in vivo using time lapse imaging and perturbation strategies. We will also use biophysical approaches in the embryo to directly test whether the cell diffusion gradient in the PSM is able to generate the forces responsible for axis elongation. We will take advantage of soft-matter physics approaches to characterize the rheological properties of the PSM which constitute important elements of the physical models. An important parameter of the models is the rate of cell addition from the TB that allows the sustained elongation movements seen during embryonic development. We will use 4D-imaging in chicken and quail transgenic embryos to quantify the flow of cells from the TB to the posterior PSM. Finally, we propose to explore the cellular and mechanical aspects of the coordination of elongation between the axial TB territory containing the PSM precursors and the forming posterior PSM to try to understand how the posterior PSM propels the TB posteriorly. The findings of this proposal should lead to an in-depth understanding of the formation of posterior tissues, an understudied aspect of vertebrate development. This work will have important implications for understanding birth defects such as caudal regression syndrome and for regenerative medicine.

项目总结/文摘