Global Patterning in Vertebrate Mesoderm

描述(申请人提供)：脊椎动物的肌肉骨骼系统，包括我们自己，由两个基本系统组成，轴向和附件。颅后轴线系统由脊椎、肋骨和相关肌肉组成，附件系统包括四肢的肌肉和骨骼及其各自的腰带。为了使生物体在运动、摄食和呼吸方面发挥正常的作用，在胚胎发育和生长过程中，这两个系统必须适当地整合。构成肌肉骨骼系统所有关键部分的细胞来自胚胎中胚层的两个种群，即体节和体细胞侧板(以下简称LP)。该项目的长期目标是确定模式基因如何影响细胞行为和形态结果，因为这两个中胚层细胞群体混合在一起，产生协调的、功能解剖结构。到目前为止，我们的工作已经在发育中的鸡胚中确定了两个动态结构域(图3)。原始域仅由体节细胞填充。远轴域由来自肌小体和结缔组织的成肌细胞组成，肌肉在这些结缔组织中分化(图1和3)。我们将这两个结构域之间的边界称为外侧闪族边界(LSF)，并假设LSF两侧的细胞由位于原始和远轴结构域的结缔组织中的独立HOX密码形成(Burke和Nowicki，2001,2003)。我们认为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。这项建议旨在完成鸡胚胎中LSF的定位，将LSF的定位扩展到哺乳动物模型系统(目标1)，并探索LSF对鸡和小鼠体壁形成的功能影响(目标2)。

DESCRIPTION (provided by applicant): The musculoskeletal system of vertebrate organisms, including ourselves, is comprised of two basic systems, the axial and the appendicle. The postcranial axial system consists of the vertebra, ribs and associated muscles, and the appendicular system includes muscles and skeleton of the limbs and their respective girdles. In order for the organism to function properly in terms of locomotion, feeding and respiration, there must be proper integration of these two systems during embryonic development and growth. The cells that form all of the key parts of the musculoskeletal system arise from two populations of embryonic mesoderm, the somites and somatic lateral plate (abbreviated here as LP). The long term goal of this project is to determine how patterning genes influence cell behavior and morphological outcome as these two mesodermal cell populations mix to produce coordinated, functional anatomy. Our work to date has identified two dynamic domains in the developing chick embryo (Figure 3). The primaxial domain is populated only by cells from the somites. The abaxial domain is made up of myoblasts from the somites and connective tissue of the LP in which the muscles differentiate (Figures 1 & 3). We have termed the boundary between the two domains the Lateral Semitic Frontier (LSF), and postulated that cells on either side of the LSF are patterned by independent Hox codes resident in the connective tissue of the primaxial and abaxial domains (Burke and Nowicki, 2001, 2003). We suggest that the LSF is the site of early information exchange that is crucial for normal patterning of the vertebrate body. This proposal seeks to complete the mapping of the LSF in the chick embryo, extend mapping of the LSF into a mammalian model system (Aim 1), and explore functional implications of the LSF for body wall formation in both chick and mouse (Aim 2).