Cellular and Molecular Mechanisms of Axial Elongation in the Mouse

脊椎动物胚胎发育的一个基本方面是将球形或盘形胚胎转变为一端有头另一端有尾的细长体。 早期胚胎组织内单个细胞的运动导致体轴的整体变窄和延伸，用细长的脊髓将头部和尾部分开。 这些细胞运动是如何组织和协调的尚不清楚，这是一个需要回答的关键问题，因为体轴伸长的失败可能导致胚胎严重畸形或死亡。 拟议中的研究将在小鼠胚胎中解决这个问题，使用携带特定基因突变的小鼠，这些突变导致体轴伸长和脊髓形成缺陷。这些突变对神经管和脊索细胞运动的影响，这两种组织有助于脊髓的形成，将使用突变和正常胚胎的延时成像来确定。 将使用蛋白质生物化学和免疫组织化学检查影响体轴伸长的神经管和脊索细胞内亚细胞和分子水平的变化。 此外，将使用遗传方法将突变靶向这些特定组织，检查单个组织（神经管，脊索，体细胞中胚层）内细胞行为对整体体轴伸长的相对贡献。 这些研究将为调节体轴形成的细胞和分子机制提供重要的新认识，并为发育过程中复杂组织运动的一般调节提供新的见解。该项目将在几个方面产生更广泛的影响。在科学层面上，它将确定身体轴伸长的关键因素，并阐明遗传和环境因素如何影响胚胎发育。 在教育方面，它将为本科生和研究生，特别是代表性不足群体的学生提供参与研究的机会，并将提供各级（高中、本科、研究生）教育使用的材料。

One of the fundamental aspects of vertebrate embryonic development is the transformation of a spherical or disc-shaped embryo into an elongated body with a head at one end and a tail at the other. Movements of individual cells within the tissues of the early embryo cause the overall narrowing and extension of the body axis, separating the head from the tail with an elongated spinal cord. How these cell movements are organized and coordinated is not known, and this is a critical question to be answered, as failure of body axis elongation can lead to severe malformations or death of the embryo. The proposed studies will address this question in mouse embryos, using mice that carry mutations in specific genes that lead to defects in body axis elongation and spinal cord formation. The effects of these mutations on cell movements in the neural tube and notochord, two tissues that contribute to the formation of the spinal cord, will be determined using time-lapse imaging of mutant and normal embryos. Changes at the subcellular and molecular level within the cells of the neural tube and notochord that affect body axis elongation will be examined using protein biochemistry and immunohistochemistry. In addition, the relative contribution of cell behavior within individual tissues (neural tube, notochord, somitic mesoderm) to overall body axis elongation will be examined using genetic approaches to target mutations to those specific tissues. These studies will provide significant new understanding of the cellular and molecular mechanisms regulating body axis formation, as well as novel insights into the general regulation of complex tissue movements during development. This project will have broader impacts in several ways. On the scientific level it will identify the key elements of body axis elongation and clarify how genetic and environmental factors may influence embryonic development. On the educational front, it will provide opportunities for both undergraduate and graduate students, particularly those from under-represented groups, to participate in research, and will provide materials for educational use at all levels (high school, undergraduate, graduate).