EMBRYONIC PHAGOCYTOSIS IN MOUSE MORPHOGENESIS

出生缺陷综合征是婴儿发病的主要原因， 死亡率在美国。 目前，只有一小部分 这些综合征是在细胞和分子水平上理解的。 为了 为了了解人类发育异常，研究人员必须描述 正常的形态发生过程 我们的长期目标是开始 通过调查了解人类出生缺陷综合征的病因 正常小鼠发育的细胞和分子机制。 医生科学家培训计划的第一阶段包括基本的 通过教学课程、实验室轮换进行科学培训， 选定的研讨会，这将作为博士学位的基础， 华盛顿大学生物结构（解剖学）系 医学院。 第一阶段培训的目的是 候选人在基础科学方面有坚实的基础，为成为 发育生物学领域的独立研究者， 人类发展 该建议的第二阶段将包括深入调查 吞噬细胞群体在正常小鼠形态发生中的作用。 四个具体的目标将被用来测试假设，正常 哺乳动物的发育依赖于一群胚胎吞噬细胞， 对巨噬细胞集落刺激因子（M-CSF）有反应，对于正常 经历细胞死亡和重塑的组织的形态发生。 这 将使用免疫组织化学和免疫组织化学方法对假设进行检验。 原位杂交定位胚胎吞噬细胞，并表征 M-CSF及其受体c-fms在4种小鼠中表达模式 菌株 研究的菌株将包括M-CSF缺陷型 op/op，以及三个在区域中具有异常程序性细胞死亡的菌株 组织重塑（CL/Fr、Os/+和Xpl）。 这些调查将 用于表征胚胎吞噬细胞、M-CSF和c-fas的作用 在正常的哺乳动物发育过程中。

Birth defect syndromes are the leading cause of infant morbidity and mortality in the United States. Currently, only a small fraction of these syndromes are understood at the cell and molecular level. In order to understand abnormal human development investigators must characterize normal morphogenetic processes. Our long-term goals are to begin to understand the etiology of human birth defect syndromes by investigating the cell and molecular mechanisms of normal mouse development. Phase I of the physician Scientist Training program consists of basic science training through didactic coursework, laboratory rotations, and selected seminars, which will serve as the basis for a Ph. D in the Department of Biological Structure (Anatomy), University of Washington School of Medicine. The purpose of this Phase I training is to give the candidate a solid foundation in basic science in preparation for becoming an independent investigator in the fields of developmental biology and human development. Phase II of this proposal will include in depth investigation into the role of a population of phagocytic cells in normal mouse morphogenesis. Four specific aims will be used to test the hypothesis that normal mammalian development relies on a population of embryonic phagocytes, responsive to macrophage colony stimulating factor (M-CSF), for normal morphogenesis of tissues undergoing cell death and remodeling. This hypothesis will be tested with the use of immunohistochemistry and in situ hybridization to localize embryonic phagocytes, and characterized the expression patterns of M-CSF and its receptor c-fms, in four mouse strains. The strains investigated will include the M-CSF deficient op/op, and three strains with aberrant programmed cell death in regions of tissue remodeling (CL/Fr, Os/+, and Xpl). These investigations will serve to characterize the role of embryonic phagocytes, M-CSF and c-fas in normal mammalian development.