Amphibian Models for Bodywall Patterning

描述(申请人提供)：到目前为止，研究人员的工作已经在发育中的脊椎动物胚胎中确定了两个动态的中胚层结构域。原始域仅由体节细胞填充。远轴域由来自肌小体和侧板结缔组织的成肌细胞组成，肌肉在其中分化。他们将这两个区域之间的边界称为外侧躯体前线(LSF)。这个新的术语避免了在提到胚胎群体时由功能术语外轴/下轴引起的混淆。研究人员已经使用鹌鹑-雏鸡嵌合体部分绘制了雏鸟体内的LSF，最近又绘制了老鼠体内的边界(Durland等人，2008年)。这些对前线的一瞥揭示了在成体形态中隐秘的背轴/原始上颌边界。有趣的是，这些神秘的结构域与不同的自然和实验小鼠突变体的影响分布是一致的。据推测，LSF是早期信息交换的场所，这对脊椎动物身体的正常模式至关重要。这里提出的工作将把我们关于LSF的知识扩展到常见的两栖动物模型，即青蛙(非洲爪哇)和火蜥蜴(Ambystoma-axolotl)系统。利用青蛙和火蜥蜴物种中新的GFP转基因技术，研究人员将首先使用同位素移植来绘制这些羊膜动物的体细胞-侧板界面，然后使用异位体节移植来验证边界代表图案边界的假设。两栖动物为直接实验方法提供了明显的优势。该项目的长期目标是建立GFP转基因两栖动物作为系统，用于检验关于重要胚胎事件期间组织相互作用的假说。医学依赖于在模型系统中外推实验结果的有效性。两栖动物物种在研究体壁形成方面的优势包括：胸壁和腹壁相对于羊膜系统相对简单，较大的细胞尺寸有利于混合血统种群的识别，以及非洲爪哇已有的丰富的分子和发育技术。更充分地了解我们所有常见模型系统中中胚层种群之间的动态相互作用将增加实验结果的相关性和价值。 叙述：这项工作研究了脊椎动物胚胎的体壁形成。形成胸腔和体壁的胚胎组织的复杂相互作用中的错误会导致人类人口中的出生缺陷。拟议的实验试图使用形态简单的两栖动物模型系统来理解中胚层组织相互作用的动力学。

DESCRIPTION (Provided by Applicant): The investigators' work to date has identified two dynamic mesodermal domains in the developing vertebrate embryo. The primaxial domain is populated exclusively by cells from the somites. The abaxial domain is made up of myoblasts from the somites and connective tissue of the lateral plate in which the muscles differentiate. They have termed the boundary between the two domains the lateral somitic frontier (LSF). This new terminology avoids the confusion caused by the functional terms epaxial/hypaxial when referring to embryonic populations. The investigators have partially mapped the LSF in the chick using quail-chick chimeras and more recently mapped the frontier in the mouse (Durland et al., 2008). These glimpses of the frontier revealed abaxial/primaxial boundaries that are cryptic in adult morphology. Interestingly, these cryptic domains are consistent with the distribution of the impact of different natural and experimental mouse mutants. It is hypothesized that the LSF is the site of early information exchange that is crucial for normal patterning of the vertebrate body. The work proposed here will extend our knowledge about the LSF into the common amphibian model, the frog (Xenopus) and salamander (Ambystoma-axolotl) systems. Taking advantage of new GFP transgenics in both frog and salamander species, the investigators will first use isotopic transplants to map the somitic-lateral plate interface in these anamniotes, and second, use heterotopic somite transplants to test the hypothesis that the frontier represents a patterning boundary. Amphibians offer distinct advantages for direct experimental approaches. The long-term goal of this project is to establish the GFP transgenic amphibians as systems for testing hypothesis about tissue interactions during important embryonic events. Medical science depends on the validity of extrapolating experimental results among model systems. The advantages of amphibian species for studying body wall formation include the relative simplicity of the thoracic and abdominal body wall relative to amniote systems, the large cell size facilitating identity of mixed lineage populations, and the abundant molecular and developmental techniques already available in Xenopus. A fuller understanding of the dynamic interactions among mesodermal populations in all of our common model systems will increase the relevance and value of experimental results. NARRATIVE: This work investigates body wall formation in vertebrate embryos. Errors in the complex interactions of the embryonic tissues that form the ribcage and body wall result in birth defects in the human population. The proposed experiments seek to understand the dynamics of mesodermal tissue interactions using morphologically simple amphibian model systems.