GDF5 coordinates bone and joint formation during digit development
GDF5 coordinates bone and joint formation during digit development
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DOI：
10.1006/dbio.1999.9241
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发表时间：
1999-05-01
影响因子：
2.7
通讯作者：
Kingsley, DM
中科院分区：
文献类型：
--
作者：
Storm, EE;Kingsley, DM
功能性骨骼系统需要许多不同组织类型的协调发展，包括软骨，骨骼，关节和肌腱。骨形态发生蛋白（BMP）家族分泌的信号分子的成员已被牵连作为骨骼发育的内源性调节剂。这是基于它们在骨和关节形成过程中的表达，它们诱导异位骨和软骨的能力，以及BMP家族成员突变动物中存在的骨骼异常。该家族的一个成员，生长/分化因子5（GDF 5），由小鼠短足症基因座编码。这种基因突变的小鼠表现出四肢骨骼长度的减少，胸骨中骨骼和关节的形成改变，以及手指中骨骼数量的减少。正常发育期间Gdf 5的表达模式以及Gdf 5和Bmp 5单突变或双突变小鼠中观察到的表型表明Gdf 5在骨骼发生中具有多种功能，包括在关节和软骨发育中的作用。为了进一步了解GDF 5在骨骼发育中的功能，我们检测了发育中的鸡和小鼠肢体对重组GDF 5蛋白的反应。这些测定的结果，再加上对短足症手指发育的分析，表明GDF 5对于软骨发育和将关节形成限制在适当位置是必要和足够的。因此，GDF 5在手指中的功能证明了软骨发育和关节发育之间的联系，并且是手指中骨骼和关节模式的重要决定因素，（C）1999 Academic Press.
A functional skeletal system requires the coordinated development of many different tissue types, including cartilage, bones, joints, and tendons. Members of the Bone morphogenetic protein (BMP) family of secreted signaling molecules have been implicated as endogenous regulators of skeletal development. This is based on their expression during bone and joint formation, their ability to induce ectopic bone and cartilage, and the skeletal abnormalities present in animals with mutations in BMP family members. One member of this family, Growth/differentiation factor 5 (GDF5), is encoded by the mouse brachypodism locus. Mice with mutations in this gene show reductions in the length of bones in the limbs, altered formation of bones and joints in the sternum, and a reduction in the number of bones in the digits. The expression pattern of Gdf5 during normal development and the phenotypes seen in mice with single or double mutations in Gdf5 and Bmp5 suggested that Gdf5 has multiple functions in skeletogenesis, including roles in joint and cartilage development. To further understand the function of GDF5 in skeletal development, we assayed the response of developing chick and mouse limbs to recombinant GDF5 protein. The results from these assays, coupled with an analysis of the development of brachypodism digits, indicate that GDF5 is necessary and sufficient for both cartilage development and the restriction of joint formation to the appropriate location. Thus, GDF5 function in the digits demonstrates a link between cartilage development and joint development and is an important determinant of the pattern of bones and articulations in the digits, (C) 1999 Academic Press.