ANALYSIS OF GROWTH CONTROL IN DEVELOPING MOUSE LIMBS

该项目的长期目标是了解 参与生长控制和模式的细胞过程 在发育中的哺乳动物四肢的形成。该系统的实验研究 类型最近已成为可能，因为 早期原位手术技术的发展 小鼠胚胎。建议进行实验，以开始一种 野生型肢体的发育分析 精选的突变体，以努力描述 与缺陷模式相关的正常生长过程。 增长将通过利用多个不同的 技术包括，BrdUrd合并以建立正常 生长参数和特定细胞类型的生日； 引入一种标记基因来追踪Small的命运 肢芽中的细胞群；生长专一性的使用 用于确定肢体生长终止模式的抗体 发展。最后，将对变异肢体进行筛查 显微外科移植致突变效应的自主性 野生型宿主胚胎。从这些信息中获得的信息 研究最终将对我们理解 先天出生缺陷，并可能对其进行矫正。在……里面 此外，了解肢体生长是如何控制的 在开发过程中可能会提供对再生能力的洞察 在更成熟的哺乳动物四肢中，生长可能会得到促进。

The long term objective for this project is to understand the cellular processes involved in growth control and pattern formation in developing mammalian limbs. Experiments of the type proposed have recently become possible due to the development of techniques for in situ surgery on early stage mouse embryos. Experiments are proposed to begin a developmental analysis of wildtype limbs and, in addition, limbs of selected mutants in an effort to characterize alterations in the normal course of growth which correlates with defective patterns. Growth will be analyzed by utilizing a number of different techniques including, BrdUrd incorporation to establish normal growth parameters and cell type-specific birthdays; the introduction of a marker gene to trace the fate of small populations of cells in the limb bud; the use of growth specific antibodies to define the pattern of growth termination during limb development. Finally, mutant limbs will be screened for autonomy of the mutational effect by microsurgical grafting onto wildtype host embryos. The information gained from these studies will ultimately be of significance to our understanding of congenital birth defects, and possibly to their correction. In addition, understanding how growth is controlled in the limb during development may provide insight into how regenerative growth may be enhanced in more mature mammalian limbs.