ANALYSIS OF GROWTH CONTROL IN DEVELOPING MOUSE LIMBS

本项目的长期目标是了解 参与生长控制和模式的细胞过程 在哺乳动物四肢发育中形成。 的实验 最近提出的类型已经成为可能，由于 早期原位手术技术的发展 小鼠胚胎 建议进行实验，以便开始 野生型肢体的发育分析，此外， 选择的突变体，以努力表征改变， 与缺陷模式相关的正常生长过程。 将通过使用一些不同的 技术包括BrdUrd掺入，以建立正常的 生长参数和细胞类型特异性生日; 引入一个标记基因来追踪小 肢芽中的细胞群;使用生长特异性 抗体，以确定肢体发育终止的模式， 发展 最后，突变的肢体将被筛选， 通过显微手术移植到 野生型宿主胚。 从这些获得的信息 研究最终将对我们理解 先天性出生缺陷，并可能对其进行纠正。 在 此外，了解肢体的生长是如何控制的， 可以让我们深入了解 在更成熟的哺乳动物肢体中，生长可能得到增强。

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.