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目的:观察骨形态发生蛋白通过Ⅰ型受体传导信号在小脑浦肯野细胞发育中的作用。为揭示临床有关骨形态发生蛋白引起的遗传病发病及治疗提供有力的依据。方法:实验于2004-03/2005-08在美国费城儿童医院Crenshaw实验室和北京大学医学部解剖学神经研究实验室完成。小鼠种类为C57Bl/6J,敲除了骨形态发生蛋白Ⅰ型受体的Bmpr1a和Bmpr1b两个亚型基因,产生了条件性的BMPR-ⅠA和经典性的BMPR-ⅠB受体敲除鼠,破坏了在小脑内的骨形态发生蛋白信号转导。并使用免疫双标calbindin,Tuj1估计小鼠胚胎13.5d和新生幼鼠的浦肯野细胞发育分化情况。结果:①在小鼠刚出生时,正常组鼠的浦肯野细胞都迁移到了小脑,并形成浦肯野细胞层;但在Bmpr1a/Bmpr1b双敲除鼠的浦肯野细胞迁移明显异常,大部分Calbindin阳性的浦肯野细胞呈簇状位于小脑深部,另有部分细胞迁移到了中脑下丘。②免疫双标显示在正常组双标的细胞位于小脑的腹侧缘;但在Bmpr1a/Bmpr1b双敲除组,双标记的浦肯野细胞数量明显减少,并且浦肯野细胞排列紊乱,说明浦肯野细胞的分化受到影响。结论:①骨形态发生蛋白信号对浦肯野细胞的作用可能不是直接的,或许是经过一些中间环节来完成的。②只有两受体基因Bmpr1a和Bm-pr1b同时敲除才能影响骨形态发生蛋白信号对小脑浦肯野细胞发育的作用。
OBJECTIVE: To observe the role of bone morphogenetic protein in the development of Purkinje cell in cerebellum via the type I receptor signaling. To reveal the clinically relevant bone morphogenetic protein-induced genetic disease incidence and treatment provide a strong basis. METHODS: The experiment was performed at Crenshaw Laboratory, Philadelphia Children’s Hospital and Peking University School of Medicine Anatomy and Neurology Laboratory from March 2004 to August 2005. The mouse type C57Bl / 6J knocked out the Bmpr1a and Bmpr1b subtypes of bone morphogenic protein type I receptor, resulting in conditional BMPR-IA and classical BMPR-IB receptor knockout mice, disrupting Bone morphogenetic protein signaling in the cerebellum. Immunocytochemistry calbindin and Tuj1 were used to estimate the development and differentiation of Purkinje cells at 13.5 days in mouse embryos and in neonatal rats. RESULTS: ① At the time of birth, Purkinje cells migrated to the cerebellum and formed Purkinje cell layer in the normal group. However, the Purkinje cell migration in the Bmpr1a / Bmpr1b double knockout mice was significantly abnormally large Some Calbindin-positive Purkinje cells are clustered in the deep part of the cerebellum, while others migrate to the mid-medial hypothalamus. ②Immunity double labeling showed that the double labeled cells in the normal group were located in the ventral margins of the cerebellum. However, in the Bmpr1a / Bmpr1b double knockout group, the number of double labeled Purkinje cells was significantly decreased and the Purkinje cells were disordered Differentiation of wild cells is affected. Conclusions: ① The effect of BMP signaling on Purkinje cells may not be direct, perhaps through some intermediate processes. ② Only the two receptor genes Bmpr1a and Bm-pr1b knock-out can affect the BMP signaling effect on the development of cerebellar Purkinje cells.