PlexinD1 deficiency induces defects in axial skeletal morphogenesis
PlexinD1 deficiency induces defects in axial skeletal morphogenesis
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DOI：
10.1002/jcb.21306
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发表时间：
2007-08-15
影响因子：
4
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
--
作者：
Kanda, Tomoatsu;Yoshida, Yutaka;Noda, Masaki
胚胎骨骼发生中的轴向模式与体节发生和血管生成的协调编程有关。如在软骨内骨形成中所见，骨骼发生与发育过程中的血管生成密切相关。丛蛋白D1是丛蛋白家族的一员，在中枢神经系统和内皮中表达，在胚胎发育过程中对血管形成和内皮定位起作用。在这里，我们研究了丛蛋白D1缺乏对骨骼发育的影响。三维显微CT检查显示PlexinD1缺陷导致轴向骨骼模式缺陷，包括椎体和肋骨形状的畸形。对椎体和长骨的组织学检查表明，PlexinD1缺乏改变了软骨的发育。丛蛋白D1缺乏并不影响相对较大的血管中的血管性血友病因子染色的水平不重视，但接近小鼠的椎体。然而，PlexinD1缺乏减少了血管性血友病因子（vWf）染色在大多数的微血管连接到椎骨。PlexinD1在新生和成年小鼠的成骨细胞和骨组织中表达。由于大多数纯合子敲除小鼠不能存活，我们研究了丛蛋白D1在接受骨髓消融的杂合子成年小鼠骨形成中的作用。然而，丛蛋白D1杂合敲除并没有显示新骨形成的缺陷。总之，丛蛋白D1参与了中轴骨骼发育的模式化。
Axial patterning in embryonic skeletogenesis associates with coordinated programming of somitogenesis and angiogenesis. As seen in endochondral bone formation, skeletogenesis is closely related to angiogenesis during development. PlexinD1 is a member of plexin family, is expressed in central nervous system and endothelium, and plays a role in blood vessel patterning and endothelium positioning during embryonic development. Here, we examined the effects of PlexinD1 deficiency on skeletogenesis. Three-dimensional micro CT examination revealed that PlexinD1 deficiency resulted in axial skeletal patterning defects including malformation in vertebral body and rib bone shape. Histological examination of the vertebral bodies and long bones showed that PlexinD1 deficiency altered the development of cartilage. PlexinD1 deficiency did not affect the levels of von Willebrand factor staining in relatively large vessels not attached but close to the vertebral body of mice. However, PlexinD1 deficiency reduced the von Willebrand factor (vWf) staining in most of the microvasculatures attached to the vertebral bone. PlexinD1 was expressed in osteoblastic cells and bone tissues of newborn and adult mice. As most of the homozygous knock out mice did not survive, we examined the role of PlexinD1 in bone formation in heterozygous adult mice subjected to bone marrow ablation. However, PlexinD1 heterozygous knockout did not reveal defects in new bone formation. In conclusion, PlexinD1 is involved in the patterning of axial skeletogenesis.