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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：
10392314
负责人：
OLIVIER POURQUIE
金额：
$ 53.57万
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/10392314
关键词：
4D Imaging Automobile Driving Behavior Biological Biomechanics Birds Body part Cancer Biology Cells Chick Embryo 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.

项目概要/摘要身体的后部逐渐由称为尾芽（TB）的结构形成。缺陷于这一过程会导致严重的出生缺陷，例如脊柱裂或尾骨发育不全。进步者后体的伸长需要产生控制结核消退的力和持续供应祖细胞来生成正在形成的组织。在之前的工作中，我们已经证明了在鸡胚中，驱动身体从 TB 伸长的过程涉及后部前成体中胚层 (PSM)，其中细胞建立随机细胞运动梯度（细胞扩散） FGF 信号传导的下游（Benazeraf 等，2010）。我们与我们的联合 PI Mahadevan 一起制定了一个新的物理框架，建议：细胞扩散的梯度产生参与伸长运动的力，就像暴露在温度梯度下的气体粒子会产生压力（Regev 等人，2017）。我们的模型基于最少数量的参数：细胞扩散梯度、细胞添加速率 PSM 和组织机械阻力，导致单向伸长力。在这里，我们将通过结合发育生物学、成像和软物质在体内测量这些参数物理学方法的目标是预测作为空间函数的胚胎伸长率和时间。我们首先提出研究细胞扩散梯度的细胞基础和 FGF 信号传导的作用使用延时成像和微扰策略在体内形成它。我们还将使用在胚胎中采用生物物理方法直接测试 PSM 中的细胞扩散梯度是否能够产生导致轴伸长的力。我们将利用软物质物理方法来表征 PSM 的流变特性，这构成了重要的物理模型的元素。模型的一个重要参数是来自 TB 的细胞添加速率，该速率允许持续胚胎发育过程中观察到的伸长运动。我们将在鸡和鹌鹑转基因胚胎来量化细胞从 TB 到后 PSM 的流动。最后，我们建议探索伸长协调的细胞和机械方面包含 PSM 前体的轴向 TB 区域和正在形成的后 PSM 之间，以尝试了解后 PSM 如何向后推动 TB。该提案的研究结果应有助于深入了解后验的形成组织，脊椎动物发育的一个尚未得到充分研究的方面。这项工作将产生重要影响用于了解出生缺陷（例如尾部退化综合症）和再生医学。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rectified random cell motility as a mechanism for embryo elongation.

纠正随机细胞运动作为胚胎伸长的机制。

DOI：
10.1242/dev.199423
发表时间：
2022
期刊：
Development (Cambridge, England)
影响因子：
0
作者：
Regev,Ido;Guevorkian,Karine;Gupta,Anupam;Pourquié,Olivier;Mahadevan,L
通讯作者：
Mahadevan,L

Dynamics of primitive streak regression controls the fate of neuromesodermal progenitors in the chicken embryo.

原始条纹回归的动力学控制了鸡胚胎中神经抑制祖细胞的命运。

DOI：
10.7554/elife.64819
发表时间：
2021-07-06
期刊：
eLife
影响因子：
7.7
作者：
Guillot C;Djeffal Y;Michaut A;Rabe B;Pourquié O
通讯作者：
Pourquié O

Direct force measurement and loading on developing tissues in intact avian embryos.

DOI：
10.1242/dev.201054
发表时间：
2023-05-01
期刊：
Development (Cambridge, England)
影响因子：
0
作者：
通讯作者：

Dynamic morphoskeletons in development.

发育中的动态形态骨架。

DOI：
10.1073/pnas.1908803117
发表时间：
2020
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Serra M
通讯作者：
Serra M

A mechanochemical model recapitulates distinct vertebrate gastrulation modes.

DOI：
10.1126/sciadv.adh8152
发表时间：
2023-12-08
期刊：
SCIENCE ADVANCES
影响因子：
13.6
作者：
Serra, Mattia;Najera, Guillermo Serrano;Chuai, Manli;Plum, Alex M.;Santhosh, Sreejith;Spandan, Vamsi;Weijer, Cornelis J.;Mahadevan, L.
通讯作者：
Mahadevan, L.